.

Вплив трансформуючого фактора росту типу beta на клітини лінії L1210 лейкемії миші з різною чутливістю до дії цисплатину: Автореф. дис… канд. біол.

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IAOe?IIAEUeIA AEAAeAI?ss IAOE OE?A?IE

?inoeooo a?io?i?? ?i. I.A. Iaeeaae?ia

ssEEIIAE* IA??ss ss?INEAA?AIA

OAeE 615.277.3:577.112.853

AIEEA O?AINOI?IOTH*IAI OAEOI?A ?INOO OEIO AAOA IA EE?OEIE E?I??
L1210 EAEEAI?? IEO? C ??CIITH *OOEEA?NOTH AeI Ae?? OeENIEAOEIO

03.00.04 – a?io?i?y

AAOI?AOA?AO

aeena?oaoe?? ia caeiaoooy iaoeiaiai nooiaiy

eaiaeeaeaoa a?ieia?/ieo iaoe

Ee?a-1999

Aeena?oaoe??th ? ?oeiien.

?iaioa aeeiiaia o a?aeae?e? ?aaoeyoe?? i?ie?oa?aoe?? ee?oei A?aeae?eaiiy
?aaoeyoi?ieo nenoai ee?oeie ?inoeoooo a?io?i?? ?i. I.A. Iaeeaae?ia IAI
Oe?a?ie.

Iaoeiaee ea??aiee –

aeieoi? a?ieia?/ieo iaoe, i?ioani?

Noieea ?inoeneaa Noaiaiiae/,

A?aeae?eaiiy ?aaoeyoi?ieo nenoai ee?oeie

?inoeoooo a?io?i?? ?i. I.A. Iaeeaae?ia IAI Oe?a?ie,

ea??aiee a?aeae?eaiiy,

caa?aeoth/ee a?aeae?eii ?aaoeyoe?? i?ie?oa?aoe?? ee?oei.

Io?oe?ei? iiiiaioe:

aeieoi? a?ieia?/ieo iaoe, i?ioani? Aaeeeee Ieeiea Ieeieaeiae/,

Euea?anueeee aea?aeaaiee oi?aa?neoao ?i. ?aaia O?aiea,

caa?aeoaa/ eaoaae?e a?io?i??;

aeieoi? iaaee/ieo iaoe Ieeioa Ieaen?e Noaiaiiae/,

ea??aiee eaai?aoi??? ai?iiiaeueii? ?aaoeyoe?? iai?io ?a/iaei ?inoeoooo
aiaeie?eiieia?? oa iai?io ?a/iaei ?i. A.I. Eii?na?aiea AII Oe?a?ie.

I?ia?aeia onoaiiaa –

?inoeooo iieaeoey?ii? a?ieia?? ? aaiaoeee IAI Oe?a?ie,

a?aeae?e iieaeoey?ii? aaiaoeee, i. Ee?a.

Caoeno a?aeaoaeaoueny “25” aeiaoiy 1999 ?ieo i 14 aiaeei? ia can?aeaii?
niaoe?ae?ciaaii? a/aii? ?aaee Ae 26.240.01 a ?inoeooo? a?io?i?? ?i. I.A.
Iaeeaae?ia IAI Oe?a?ie (252601, Ee?a-30, aoe. Eaiioiae/a, 9)

C aeena?oaoe??th iiaeia iciaeiieoeny o a?ae?ioaoe? ?inoeoooo a?io?i??
?i. I.A. Iaeeaae?ia IAI Oe?a?ie (i. Ee?a, aoe. Eaiioiae/a, 9)

Aaoi?aoa?ao ?ic?neaiee “16” aa?aniy 1999 ?.

A/aiee nae?aoa? niaoe?ae?ciaaii? a/aii? ?aaee

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fffffffffffffffffffedc6b000000004bb1d17c00000000003ddfffffffffffffffffff
fffffffffffff8e4cb922400000000000000005feafeffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff0000
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffc51b0000000024a0a300000000
0000baf8fffffffffffffffffffffffffffffffef8eac5ac81430000023581d6feffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
fffffffffffffffffffffffffffffffffffffffffffffffffffffbffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffff0000ffffffffffffffffffffffffffffffffffffffffffffffff
fffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff6
b42f00000000005f2700000000007cf8fffffffffffffffffffffffffffffffffffef8f8
f3dfd1babad6f0feffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
fffff3feffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffff0000ffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
fffffffffffffffffffffffff0c26b000000000000000000000054f0feffffffffffffff
fffffffffffffffffffffffffffffff8f6feffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
fffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff6ffffffffff
fffffffffffffffffffffffffef3ffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff0000
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
fffffffffffffffffffffffffffffffffffffffffffffffff8f6d3430000000000000000
000062fbffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
fffffffffffffffffffffffffffffffffffffffeffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffedeaffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffff0000ffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
fffff0c55a00000000000000000079ffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
fef8fffffffffffffffffffffffffffffefbffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffff0000ffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
fffffffffffffffffffffffffffffff6d6a9400000000000000092ffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffeae4ffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff0000
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
fffffffffffffffffffffffffffffffffffffffffffffffffffffffffeeabd4900000000
0000c0ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
fffffffffbfbffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffff0000ffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
fffffffffffff8d9922900000049eaffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffff0000ffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
fffffffffffffffffffffffffffffffffffffffbeac8794e76c8ffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
fffffffffffffffffbffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff0000
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
fffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff6feeae2
e4fbffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffff0000ffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
fffffffffffffffffffffffeffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffff0000ffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff0000
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffff0000ffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffff0000ffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff0000
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffff0000ffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffff0000ffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff
ffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffffff0000
0400000007010100030000000000

eaiaeeaeao a?ieia?/ieo iaoe E??naiei I.A.

17

CAAAEUeIA OA?AEOA?ENOEEA ?IAIOE

Aeooaeuei?noue oaie. I?ae /an o?i?ioa?aiaaoe/iiai e?eoaaiiy oai?eo ?c
ceiye?nieie iiaiooai?aiiyie ana /ano?oa aeyaeythoueny iooeeii? ee?oeie,
no?ee? aei ae?? canoiniaoaaieo i?aia?ao?a. Ca aeaieie Kerbel, 1997, oaea
iaaooa ?acenoaioi?noue ?icaeaa?oueny iaeaea o 30% oai?eo, ye?
i?aeaeaaaeeny o?i?ioa?ai??. Oiio aeooaeueiei ? aea/aiiy iaoai?ci?a
?acenoaioiino? ee?oei aei ae?? ie?aieo i?ioeiooeeiieo i?aia?ao?a c oei,
uia ia?aoeiaeeoe oeueiio iaaaoeaiiio i?ioeano ? oieeiooe aeei?enoaiiy
iaaoaeoeaieo e?e?a.

Oeenieaoei oe?iei canoiniao?oueny aeey e?eoaaiiy oai?eo ia ea?oeeiiie
y?/iee?a, iiei/ii? caeice, oeoiea, eeoe?aieea, na/iaiai i?oo?a, iooeeie
aieiae oa oe?, aaiiaeanoice. Aaaaeathoue, ui oeeoioiene/ia ae?y oeueiai
i?aia?aoo ia ee?oeie coiiaeaia eiai eiaaeaioiei ca’ycoaaiiyi c AeIE c
ooai?aiiyi iaeii- ? aeaieaioethaiaeo coeaie AeIE oa coeaie AeIE c
a?eeaie [Chu, 1994]. Aiane?aeie oaeiai iioeiaeaeaiiy AeIE ee?oeie
iiaeooue aeiooe oeyoii aiiioico [Sorenson, et al., 1990, Henkels and
Turchi, 1997].

E?eoaaiiy oeenieaoeiii, ye ? ?ioeie i?ioeiooeeiieie i?aia?aoaie, iiaea
aeeeeeaoe ?icaeoie ?acenoaioiino? ceiye?nieo ee?oei aei eiai ae??.
Ia?aaaaeii ??aaiue oaei? ?acenoaioiino? ia ia?aaeuo? 50 ?ac?a, oi/a ?
aeai? i?i ?nioaaiiy ee?oei, ye? a 1000 ?ac?a no?ee?o? aei ae??
oeenieaoeio, i?ae ?o aaouee?anuee? iiia?aaeieee. Iaiao?aeii cacia/eoe,
ui iaa?oue iacia/ia i?aeaeuaiiy ?acenoaioiino? iooeei aei oeenieaoeio ?
na?eiciith ee?i?/iith i?iaeaiith, ine?eueee ca?eueoaiiy aeice i?aia?aoo
i?ae /an e?eoaaiiy iiaea aeeeeeaoe ?icaeoie ie?eiai? iaaeinoaoiino?,
ia?eoa??eio iae?iiao?th, aeooioo, e?iaioa/? oa ?io? iaoieia?/i? noaie
[Chu, 1994].

? aeai?, ui ?acenoaioi?noue iooeeiieo ee?oei aei ae?? oeenieaoeio iiaea
caaacia/oaaoeny e?eueeiia ??cieie iaoai?ciaie, a naia: 1) ciaioaiiyi
iaa?iiaaeaeaiiy i?aia?aoo a ee?oeiao; 2) i?aeaeuaiiyi
aioo??oiueiee?oeiiiai ??aiy aeooao?iio aai aeoeaiino?
aeooao?ii-S-o?ainoa?ace; 3) c?inoaiiyi ai?noo aioo??oiueiee?oeiieo
iaoaeio?iia?i?a; 4) iineeaiiyi i?ioean?a ?aia?aoe?? AeIE o ee?oeiao; 5)
iioeiaeaeaiiyi iaoai?ci?a aiiioe/ii? caaeaae? ee?oei [Oeoiaa e *aooi,
1998; Segal-Bendirdjian, et al., 1998]. Iaeiae, aeiaeai c oeeo
iaoai?ci?a ia ? oi?aa?naeueiei.

A inoaii? ?iee c?inoa? e?euee?noue aeaieo i?i o/anoue neaiaeueieo oeyo?a
iie?iaioeaeieo oaeoi??a ?inoo a ?aaoeyoe?? a?aeiia?ae? ceiye?nieo ee?oei
ia ae?th ??cieo o?i?ioa?aiaaoe/ieo i?aia?ao?a, oi/a io?eiai? ?acoeueoaoe
? aeineoue noia?a/eeaeie. Iieacaii, ui ai?aea?iaeueiee oaeoi? ?inoo
(AO?), o?ainoi?ioth/ee oaeoi? ?inoo (OO?) oeio iineeththoue oiene/io
ae?th oeenieaoeio uiaei ee?oei e?i?? MDA-468 ?aeo iiei/ii? caeice, a
cieaeaiiy ??aiy aeni?an?? oeeie ee?oeiaie ooieoe?iiaeueiiai ?aoeaioi?a
AO? i?ecaiaeeoue aei i?eieiaiiy oaeiai aoaeoo [Dixit, et al., 1997].
Iaeiae, o ee?oeiao oe??? iooeeie e?i?? MCF-7, ?acenoaioieo aei ae??
aeieni?oa?oeeio, aeyaeaii i?aeaeuaio e?euee?noue ?aoeaioi??a AO? o
ii??aiyii? c ?o /ooeeaeie iiia?aaeieeaie [Wosikowsky, et al., 1997]. O
ee?oeiao e?i?? AIO6 iooeeie iiei/ii? caeice, ?acenoaioieo aei ae??
oeenieaoeio ? oeeeeioinoai?aeo, cao?eniaaii i?aeaeuaiee ??aaiue OO?
[Teicher, et al., 1997]. Aeaei?ei, yeee ? ?ia?a?oi?ii ae?? OO?, aeeeeeaa
i?aeoe/ii iiaio ao?aoo oaei? ?acenoaioiino?. A ?ioeo aeine?aeaeaiiyo
aoei iieacaii, ui OO?1 iineeth? eaoaeueio ae?th oeenieaoeio ia ee?oeie
e?i?? A549 ea?oeeiiie eaaai?a ethaeeie oa ai?oae?aeuei? ee?oeie e?i??
Mv1Lu eaaai?a ii?ee [Raynal, et al., 1997].

Iieaeoey?i? iaoai?cie, ye? iiina?aaeeiaothoue aeioe/i?noue oeyo?a
ia?aaea/? neaiaeo OO? c iaoai?ciaie ?acenoaioiino? ceiye?nieo ee?oei aei
ae?? i?ioeiooeeiieo i?aia?ao?a, cie?aia oeenieaoeio, caeeoathoueny
iaeiaea/aieie. C’ynoaaiiy oaeeo ca’yce?a iiaea caaacia/eoe iniiao aeey
?ic?iaee iiaeo, aoaeoeai?oeo i?aeoiae?a o iiaeieaii? ?acenoaioiino?
iooeeiieo ee?oei aei ae?? i?ioeiooeeiieo i?aia?ao?a c iaoith ?o
ciaoeiaeaeaiiy oa aeey i?aeaeuaiiy no?eeino? ii?iaeueieo ee?oei
i?aai?cio i?ae /an canoinoaaiiy o?i?ioa?ai??.

Ca’ycie ?iaioe c iaoeiaeie i?ia?aiaie, ieaiaie, oaiaie. Aeena?oaoe?eia
?iaioa aeeiiaia o a?aeae?e? ?aaoeyoe?? i?ie?oa?aoe?? ee?oei A?aeae?eaiiy
?aaoeyoi?ieo nenoai ee?oeie ?inoeoooo a?io?i?? ?i. I.A. Iaeeaae?ia IAI
Oe?a?ie ca?aeii c ieaiii iaoeiai-aeine?aeii? ?iaioe ca oaiith
“Aeine?aeaeaiiy ?ie? iie?iaioeaeieo oaeoi??a ?inoo o a?aeiia?ae?
ii?iaeueieo ? iooeeiieo ee?oei ia ae?th no?aniaeo /eiiee?a” (?
aea?ae?a?no?aoe?? 01970004658).

Iaoa ? caaaeaiiy aeine?aeaeaiiy. Aieiaiith iaoith ?iaioe aoei
aeine?aeeoe iaoai?cie ca’yceo i?ae ?acenoaioi?noth ee?oei e?i?? L1210
eaeeai?? ieo? aei ae?? i?ioeiooeeiiiai i?aia?aoo oeenieaoeio oa ?o
/ooeea?noth aei ?aaoeyoi?iiai aieeao o?ainoi?ioth/iai oaeoi?a ?inoo 1.
Aeey aeinyaiaiiy oe??? iaoe o aeena?oaoe?ei?e ?iaio? ae??ooaaee ianooii?
caaaeaiiy:

1) ii??aiyoe aieea OO?1 ia i?ie?oa?aoe?th oa aiiioic ee?oei e?i?? L1210,
/ooeeaeo oa ?acenoaioieo aei oeeoioiene/ii? ae?? oeenieaoeio;

2) ii??aiyoe aeni?an?th aieiaieo eiiiiiaio?a neaiaeueiiai oeyoo OO?,
oaeeo ye niaoeeo?/i? ?aoeaioi?e oa a?eee Smad – aioo??oiueiee?oeii?
i?ia?aeieee ?aaoeyoi?iiai neaiaeo oeueiai oeeoie?ia – o ee?oeiao e?i??
L1210 c ??ciith /ooeea?noth aei ae?? oeenieaoeio;

3) aeine?aeeoe aieea ia ee?oeie e?i?? L1210, ye? aeyaeythoue ??cio
/ooeea?noue aei ae?? oeenieaoeio, oaeeo /eiiee?a, ye oeeoioiene/i?
eaeoeie oa a?ia?oa?i?y;

4) aeine?aeeoe aoaeaaiaei? aeaoa?i?iaioe iiaa?oi? ee?oei e?i?? L1210 c
??ciith /ooeea?noth aei ae?? oeenieaoeio ca aeiiiiiaith ie?aieo
eaeoei?a.

Iaoeiaa iiaecia iaea?aeaieo ?acoeueoao?a.

1. Aia?oa anoaiiaeaii, ui ?acenoaioi?noue ee?oei e?i?? L1210 eaeeai??
ieo? aei i?ioeiooeeiiiai i?aia?aoo oeenieaoeio ni?aiaaea? c ?o
no?ee?noth aei ae?? OO? ye ?ia?a?oi?a ?inoo oa ?iaeoeoi?a aiiioico.

2. Aia?oa iieacaii, ui ao?aoa /ooeeaino? aei ae?? OO? o ?acenoaioieo aei
oeenieaoeio ee?oei e?i?? L1210 ? anioe?eiaaiith c nooo?aei cieaeaiiyi o
ieo ??aiy aeni?an?? niaoeeo?/ieo ?aoeaioi??a ? oeio OO? oa iineeaiiyi
aeni?an?? ?ia?a?oi?iiai a?eea Smad6, yeee ia?aoeiaeaea? ia?aaea/?
?aaoeyoi?iiai neaiaeo OO? o ee?oeiao-i?oaiyo. Aeni?an?y ?ioeo a?ee?a
Smad (Smad2, Smad3, Smad4, Smad7) o ee?oeiao c ??ciith /ooeea?noth aei
ae?? oeenieaoeio ? iiae?aiith.

3. Aeyaeaii a?aei?iiino? o neeaae? ae?eii?ioa?i?a ieaciaoe/ieo iaia?ai
i?ae ee?oeiaie e?i?? L1210, ?acenoaioieie aei ae?? oeenieaoeio, oa ?o
/ooeeaeie iiia?aaeieeaie. Cie?aia, a?aecia/aii iineeaio aeni?an?th o
?acenoaioieo ee?oei oe??? e?i?? iaia?aiiiai ae?eii?ioa?ia iieaeoey?iith
ianith aeecueei 240 eAea, yeee aca?iiae?? c eaeoeiii a?ao?no Arachis
hypogaea (PNA).

4. Iieacaii, ui ?acenoaioi? aei oeenieaoeio oa OO? eaeeai?/i? ee?oeie
e?i?? L1210 ? /ooeeaeie aei ae?? aeayeeo oeeoioiene/ieo eaeoei?a oa
a?ia?oa?i??.

I?aeoe/ia cia/aiiy iaea?aeaieo ?acoeueoao?a. Io?eiai? o ?iaio? aeai? i?i
iaoai?cie ii?ooaiiy neaiaeueieo oeyo?a OO? o ee?oeiao eaeeai??, ye?
oa?aeoa?ecothoueny i?aeaeuaiith ?acenoaioi?noth aei oeeoioiene/ii? ae??
i?ioeiooeeiiiai i?aia?aoo oeenieaoeio, iiaeooue aooe aenia?eiaioaeueiith
iniiaith aeey ?ic?iaee iiaeo i?aeoiae?a o o?i?ioa?aiaaoe/iiio e?eoaaii?
iieieia?/ieo oai?eo c i?aeaeuaiith no?ee?noth aei oeueiai i?aia?aoo.
E??i oeueiai, o oaeeo aeiaaeeao iiaea aooe ei?eniei canoinoaaiiy
aaethoei?io 1 c iiaee (VAA-1) oa eieaeueii? a?ia?oa?i?? iooeeie.

?acoeueoaoe, ui noinothoueny ?iaeoeoe?? aiiioico iooeeiieo ee?oei i?ae
ae??th ie?aieo o?i?ioa?aiaaoe/ieo i?aia?ao?a oa oeeoie?i?a iiaeooue
aeei?enoiaoaaoeny o niaoeeo?nao c ee?oeiii? a?io?i?? ia a?ieia?/ieo
oaeoeueoaoao oi?aa?neoao?a.

Iniaenoee aianie caeiaoaa/a. ?iaioa aeeiiaia aeena?oaioii naiino?eii ca
aeiyoeii aiae?co ae?eii?ioa?i?a iiaa?oi? ee?oei c aeei?enoaiiyi
eaeoei?a, yeee cae?enithaaany ni?eueii c ae.a.i. Eooeeeii I.Ae.,
e.oa?i.i. Aioiitheii A.I. oa e.a.i. Noaneeii O.A.

Ai?iaaoe?y ?acoeueoao?a aeena?oaoe??. Iaoa??aee aeena?oaoe??
aeiiia?aeaeeny ia eiioa?aioe?? iieiaeeo a/aieo a ?inoeooo?
aenia?eiaioaeueii? iieieia??, iaoieia?? ? ?aae?ia?ieia?? ?i. ?.?.
Eaaaoeueeiai IAI Oe?a?ie (Ee?a, 1997), ia 6-e eiioa?aioe??
?a?iiaenueeiai oiaa?enoaa aiae?oe/ii? ee?oeiii? iaoieia??
(Aaeaeaeueaa?a, I?ia//eia, 1999) ? ia i?aeia?iaei?e eiioa?aioe??
INTERLEC 18 (Ii?onioo, Aaeeeia?eoai?y, 1999).

Ioae?eaoe??. Ca iaoa??aeaie aeena?oaoe?? iioae?eiaaii 7 iaoeiaeo
i?aoeue, c ieo 5 noaoae.

No?oeoo?a ? ia’?i aeena?oaoe??. Aeena?oaoe?y neeaaea?oueny c? anooio,
/ioe?ueio ?icae?e?a (iaeyae e?oa?aoo?e, iaoiaee aeine?aeaeaiue,
?acoeueoaoe aeine?aeaeaiue, iaaiai?aiiy ?acoeueoao?a), aeniiae?a oa
nieneo aeei?enoaieo aeaea?ae, yeee i?noeoue 261 iaeiaioaaiiy. ?iaioa
aeeeaaeaia ia 155 noi??ieao, i?i?ethno?iaaia 41 ?enoieii ? 1 oaaeeoeath.

INIIAIEE CI?NO

Iaeyae e?oa?aoo?e. Iienai? iieaeoey?i? iaoai?cie, aiane?aeie ii?ooaiiy
yeeo a?aeaoaa?oueny o?ainoi?iaoe?y ii?iaeueieo ee?oei o iooeeii?.
Aena?oeai? iaoai?cie ?iaeoeoe?? aiiioe/ii? caaeaae? ee?oei,
iioeiaeaeaiiy yeeo ? iaei??th c i?e/ei ?o ceiye?nii? o?ainoi?iaoe??.
Iaaaaeai? aeai? i?i i?e/eie aeieeiaiiy ?acenoaioiino? ceiye?nieo ee?oei
aei ae?? i?ioeiooeeiieo i?aia?ao?a, cie?aia aei oeenieaoeio. Cia/ia
oaaaa i?eae?eaia ?icaeyaeia? no?oeoo?e, ?aoeaioi??a ? neaiaeueiiai oeyoo
ae?? OO? – oe?iei?iciianthaeaeaiiai oeeoie?ia, yeee aa?a o/anoue o
?aaoeyoe?? i?ie?oa?aoe??, aeeoa?aioe?aoe?? oa aiiioico ee?oei. Ie?ai?
?icae?ee i?enay/ai? iieno iaoai?ci?a ae?? ia ee?oeie ?ineeiieo eaeoei?a
oa a?ia?oa?i??.

Iaoiaee aeine?aeaeaiue. Ia’?eoii aeine?aeaeaiue aoee ee?oeie e?i?? L1210
eaeeai?? ieo? oa ee?oeie noae?i?? L1210/R c i?aeaeuaiith ?acenoaioi?noth
aei ae?? i?ioeiooeeiiiai i?aia?aoo oeenieaoeio. Aeei?enoai? o ?iaio?
ee?oeie aoee io?eiai? c Eieaeoe?? ee?oeiieo eoeueoo? ?inoeoooo
aenia?eiaioaeueii? iaoieia??, iieieia?? oa ?aae?ia?ieia?? ?i. ?.?.
Eaaaoeueeiai IAI Oe?a?ie. Ee?oeie ae?iuoaaee a na?aaeiaeu? ?aea,
iiaeeo?eiaaiiio Aeaeueaaeei (AeIA), o i?enooiino? 10% ne?iaaoee e?ia? c
aia??ii?a aaeeei? ?iaaoi? ooaeiae (NE) ? aioea?ioeea aaioai?oeeio (50
iea/ie).

I?ie?oa?aoeaio aeoeai?noue ee?oei aecia/aee: 1) oeyoii i?ae?aooieo ?o
e?eueeino? a eaia?? Ai?y?aa ? aecia/aiiy a?aenioea ia?oaeo ee?oei o
oano? c aeei?enoaiiyi o?eiaiiaiai neiueiai; 2) ca aeeth/aiiyi
3I-oei?aeeio a AeIE ee?oei; 3) ca e?euee?noth ooai?aieo eieii?e o
na?aaeiaeu?, ui i?noeei 0,33% aaa?o [Rizzino, 1987].

Oeeoioiene/i?noue aeine?aeaeoaaieo ?a/iaei aecia/aee, aeiaeath/e ?o aei
eoeueoo?aeueiiai na?aaeiaeua o i?enooiino? 10% NE. Aeey aea/aiiy aieeao
OO?1 ee?oeie iiia?aaeiuei aeo?eioaaee 24 aiae o na?aaeiaeu? AeIA aac NE,
i?ney /iai aeiaeaaaee oeeoie?i ? NE (5%). Aeey aea/aiiy aieeao
a?ia?oa?i?? ee?oeie i?ia??aaee ia aiaeyi?e aai? i?e 42 aai 43 0N ? i?ney
oeueiai ?ieoaoaaee i?e 37 0N.

Aiiioe/i? ee?oeie aeyaeyee ca oa?aeoa?iith o?aaiaioaoe??th AeIE, yeo
aeae?eyee ? ?icae?eyee iaoiaeii aeaeo?ioi?aco a 1% aaa?iciiio aae?
[Eoae?yaaoe e ae?., 1996]. AeIE oa?aoaaee aoeae?e a?ii?aeii, yeee
aeiaeaaaee a aeaeo?iaeiee aooa? aei e?ioeaai? eiioeaio?aoe?? 2 iea/ie.
Ciie AeIE ia aeaeo?ioi?aa?ai? aeyaeyee a oeueo?ao?ieaoiaiio
aei?ii?ithaaii?.

Aeey aeine?aeaeaiiy aeni?an?? eiiiiiaio?a neaiaeueiiai oeyoo OO? a?eee
e?cao?a ee?oei ? iaia?aiii? o?aeoe?? ?icae?eyee aeaeo?ioi?aoe/ii a
iie?ae?eeai?aeiiio aae? (IAAA) ca iaoiaeii Eaiie? [Laemmli, 1970] ?
ia?aiineee ia i?o?ioeaetheicio iaia?aio. ?aoeaioi?e ? ? ?? oeio OO? oa
a?eee Smad ?aeaioeo?eoaaee ca aeiiiiiaith niaoeeo?/ieo aioeo?e,
etha’ycii iiaea?iaaieo aeieoi?ii Nooaeueieoeueeei N.?. (Ethaea?a?anueeee
?inoeooo ?aeo, Oaaoe?y). I?noey ca’ycoaaiiy aioeo?e aeyaeyee ca
aeiiiiiaith iaoiaeo oai?ethi?ianoeaioe??. Eiioeaio?aoe?th a?eea a i?iaao
aecia/aee ca iaoiaeii Iaoa?niia [Peterson, 1977].

Eiioeaio?aoe?th OO?1 o eiiaeeoe?iiiaaieo ee?oeiaie eoeueoo?aeueieo
na?aaeiaeuao aecia/aee ca aeiiiiiaith iaai?o aeey e?euee?nii? aeaoaeoe??
OO?1 Quantikine (“R&D Systems”, NOA).

Ae?eiceeuei? aeaoa?i?iaioe iiaa?oi? ee?oei aeine?aeaeoaaee ca: 1)
aaethoeiaoe??th ee?oei eaeoeiaie [Oeaaaeueneee e ae?., 1989]; 2)
ca’ycoaaiiyi eaeoei?a c ee?oeiaie c aeei?enoaiiyi oeeoio?i?/ieo iaoiae?a
[Eooeee e ae?, 1989]; 3) ca’ycoaaiiyi eaeoei?a, i?/aieo ia?ieneaeacith
o?iio, c a?eeaie ee?oeiieo iaia?ai, ?icae?eaieo aeaeo?ioi?aoe/ii ?
ia?aianaieo ia i?o?ioeaeetheicio iaia?aio.

Noaoenoe/io ia?iaeo cae?enithaaee ca ?acoeueoaoaie 3-4 aenia?eiaio?a c
o?ueiia iiaoi?aie o eiaeiiio aa??aio?. Na?aaei? cia/aiiy “I” ? na?aaeith
iioeaeo “m” ?ic?aoiaoaaee, ye iienaii a [Ni??i, Aeiia?aaeiaa, 1975].
Ii??aiyiiy aeaio i?ieeaeo aaee/ei i?iaiaeeee ia iniia? iieacieea
a??ia?aeiino? ??cieoe? “t” (e?eoa??e No’thaeaioa). A?aei?ii?noue i?ae
aaee/eiaie aaaaeaee aeinoia??iith, eiee ?iia??i?noue ??cieoe? ? aoea
iaioith 0,05.

?acoeueoaoe aeine?aeaeaiue oa ?o iaaiai?aiiy

Aieea OO?1 ia i?ie?oa?aoe?th ee?oei e?i?? L1210 c ??ciith /ooeea?noth
aei ae?? oeenieaoeio

? aeai?, ui OO? ?ia?ao? ??no oa ?iaeoeo? aiiioic ee?oei e?i?? L1210
[Motyl, 1998], oiae? ye ee?oeie oe??? e?i??, ?acenoaioi? aei
oeenieaoeio, oaeiio aeine?aeaeaiith ia i?aeaeaaaeeny. Ie ii??aiyee
/ooeea?noue ee?oei noae?i?? L1210 oa ee?oei aeo?aeii? e?i?? aei ae??
OO?1.

Anoaiiaeaii, ui OO?1 aeinoia??ii cieaeo? ??aaiue aeeth/aiiy 3I-oei?aeeio
a AeIE ee?oei e?i?? L1210. I?e eiioeaio?aoe?? OO?1 10 ia/ie aeeth/aiiy
?aae?iaeoeaii? i?oee noaiiaeoue 66% a?ae ??aiy eiio?ieth. Oeae aoaeo ia?
aeicicaeaaeiee oa?aeoa?. O oie aea /an ??aaiue aeeth/aiiy 3I-oei?aeeio a
AeIE ee?oei noae?i?? L1210/R i?aeoe/ii ia ci?ith?oueny iaa?oue i?e
eiioeaio?aoe?? OO?1 50 ia/ie.

A ?ioiio aeine?ae? iieacaii, ui OO?1 o eiioeaio?aoe?? 5 ia/ie neeueii
?ia?ao? i?ie?oa?aoe?th ee?oei e?i?? L1210 (?en. 1a). Oae, i?ney 4 ae?a
?ieoaaoe?? e?euee?noue ee?oei, ye? ?inee o i?enooiino? aeaiiai
oeeoie?ia, ? a o?e ?ace ieae/ith, i?ae o eiio?ie?. ??no ee?oei noae?i??
L1210/R i?aeoe/ii ia ci?ith?oueny i?ae aieeaii oaeeo eiioeaio?aoe?e OO?1
(?en. 1a).

OO?1 aeyaey? ?ia?aoth/ee aieea ia ??no ee?oei e?i?? L1210 o na?aaeiaeu?,
ui i?noeoue 0,33% aaa?o. Oae, aeaiee oeeoie?i o eiioeaio?aoe?? 5 ia/ie
ia 46% cieaeo? e?euee?noue eieii?e, ooai?aieo ee?oeiaie e?i?? L1210, aea
ia ci?ith? ??aiy eieii??ooai?aiiy ee?oei noae?i?? L1210/R. Iaiao?aeii
cacia/eoe, ui OO?1 iineeth? ?ia?aoth/ee aieea oeenieaoeio ia ??no a
aaa?eciaaiiio na?aaeiaeu? ee?oei e?i?? L1210 ? i?aeoe/ii ia aieeaa? ia
ae?th oeueiai i?aia?aoo o aeiaaeeo ee?oei noae?i?? L1210/R.

?en. 1

Aieea OO?1 ia ??no ee?oei e?i?? L1210 (a) ? noae?i?? L1210/R (a):

– eiio?ieuei? ee?oeie; – o i?enooiino? OO?1 (5 ia/ie).

Ioaea, ia i?aenoaa? oeeo aeaieo iiaeia c?iaeoe aeniiaie, ui ee?oeie
noae?i?? L1210/R, ye? ? no?ee?oeie aei ae?? oeenieaoeio, aeyaeythoue
?acenoaioi?noue aei ??no?ia?aoth/iai aieeao OO?. Iaiao?aeii
i?aee?aneeoe, ui oea ia?oee aeyaeaiee i?eeeaae iiceoeaii? ei?aeyoe??
i?ae ?acenoaioi?noth iooeeiieo ee?oei aei ae?? oeenieaoeio oa ?o
no?ee?noth aei ?ia?aoaaiiy OO?.

?iaeoeoe?y aiiioico i?ae aieeaii oeenieaoeio ? OO?1 o ee?oeiao e?i??
L1210 c ??ciith /ooeea?noth aei ae?? oeenieaoeio

?ia?aoth/a ae?y oeenieaoeio ? OO? ia ee?oeie e?i?? L1210 iiaea aooe
coiiaeaia ?iaeoeoe??th a ieo aiiioico [Sorenson, et al., 1990; Motyl,
1998]. Aaaaea?oueny, ui ii?ooaiiy iaoai?ci?a aiiioe/ii? caaeaae? ?
iaei??th c i?e/ei ?acenoaioiino? ceiye?nieo ee?oei aei ae?? oeenieaoeio
[Segal-Bendirdjian, et al., 1995]. Ie ii??aiyee caeaoi?noue oeenieaoeio
? OO?1 ?iaeoeoaaoe aiiioic o ee?oeiao e?i?? L1210 oa noae?i?? L1210/R.

sse aeaeii c ?acoeueoao?a, iaaaaeaieo ia ?en. 2, OO?1 (5 ia/ie) oa
oeenieaoei (0,1 iea/ie) ?iaeoeothoue aiiioic o ee?oeiao e?i?? L1210. O
oie naiee /an i? OO?1 (5 ia/ie), i? oeenieaoei (1 iea/ie) ia
aeeeeeathoue o?aaiaioaoe?? AeIE, oa?aeoa?ii? aeey aiiioico, o ee?oeiao
noae?i?? L1210/R.

?en. 2

Aeaeo?ioi?aa?aia AeIE ee?oei e?i?? L1210 (1,2,3) oa noae?i?? L1210/R
(4,5,6): 1,4 – eiio?ieuei? ee?oeie; 2,5 – i?ney ?ieoaaoe?? i?ioyaii 48
aiae o i?enooiino? OO?1; 3,6 – i?ney ?ieoaaoe?? i?ioyaii 48 aiae o
i?enooiino? oeenieaoeio; 7 – ia?ea?e iieaeoey?ii? iane o?aaiaio?a AeIE.

Aeine?aeaeaiiy neaiaeueiiai oeyoo OO? oa eiai i?iaeoeoe?? o ee?oeiao
e?i?? L1210 c ??ciith /ooeea?noth aei ae?? oeenieaoeio

Uia c’ynoaaoe iaoai?cie ?acenoaioiino? ee?oei noae?i?? L1210/R aei ae??
OO?, ie aeine?aeeee aeni?an?th eiiiiiaio?a neaiaeueiiai oeyoo oeueiai
oeeoie?ia. A?aeiii, ui aca?iiae?y OO? c? niaoeeo?/ieie ee?oeiieie
?aoeaioi?aie aeeeeea? ?o aeoeaaoe?th. A?ae iiaa?oiaaeo ?aoeaioi??a OO?
aei yae?a ee?oeie-i?oai? neaiae ia?aaea?oueny a?eeaie Smad. A?eee Smad2
? Smad3 aaciina?aaeiuei aca?iiae?thoue c aeoeaiaaieie ?aoeaioi?aie ?
oinoi?eeththoueny ieie. A?eie Smad4 aca?iiae?? c oinoi?eeueiaaieie
a?eeaie Smad2 ? Smad3, ooai?thth/e eiiieaen, yeee ia?aiineoueny a yae?i,
aea aa?a o/anoue a aeoeaaoe?? o?aine?eioe??. Ooieoe?th ?ia?a?oi??a
?aaoeyoi?iiai neaiaeo OO? a ee?oei? aeeiiothoue a?eee Smad6 ? Smad7
[Derynk and Feng, 1997; Massague, 1998].

Iaoiaeii Western-aeio aiae?co c aeei?enoaiiyi niaoeeo?/ieo aioeo?e ie
iieacaee, ui ee?oeie e?i?? L1210 c ??ciith /ooeea?noth aei ae??
oeenieaoeio a?ae??ciythoueny ca ??aiai aeni?an?? ?aoeaioi?a ? oeio OO?
(?en. 3). Oeae a?eie i.i. 55 eAea aeia?a aeyaey?oueny o iaia?aiieo
i?aia?aoao, io?eiaieo c aaouee?anueeeo ee?oei e?i?? L1210, ? aeoaea
neaai aeni?ano?oueny o iaia?aiao ee?oei noae?i?? L1210/R. O oie naiee
/an ?aoeaioi?e ?? oeio /?oei aeyaeythoueny a iaia?aiieo i?aia?aoao ye
aaouee?anueeeo, oae ? ?acenoaioieo aei ae?? oeenieaoeio ee?oei e?i??
L1210 (?en. 3).

?en. 3

Aeni?an?y ?aoeaioi??a OO? oeio ? (TRI) ? oeio ?? (TRII) o ee?oeiao e?i??
L1210 (1,3) oa noae?i?? L1210/R (2,4).

sse o ee?oeiao e?i?? L1210, oae ? a ee?oeiao noae?i?? L1210/R
aeni?anothoueny a?eee Smad2, Smad3, Smad4, Smad6 ? Smad7, ye?
iiaeoeththoue ia?aaea/o ?aaoeyoi?iiai neaiaeo OO?. Iaie ia aeyaeaii
a?aei?iiinoae a aeni?an?? a?ee?a Smad2, Smad3 ? Smad4 i?ae
aaouee?anueeeie, /ooeeaeie aei oeenieaoeio ee?oeiaie, oa ?acenoaioieie
aei ae?? oeueiai i?aia?aoo ee?oeiaie noae?i?? L1210/R (?en. 4). Oae?
/eiieee, ye OO?1 (5 ia/ie, 1 aiae), oeenieaoei (1 iea/ie aeey ee?oei
e?i?? L1210, 10 iea/ie aeey ee?oei noae?i?? L1210/R, 24 aiae) ? VAA-1 (5
ia/ie, 24 aiae) nooo?ai ia ci?iththoue aeni?an?? oeeo a?ee?a o
aeine?aeaeoaaieo ee?oeiao (?en. 4). Aeine?aeaeaiiy aieeao aeacaieo
aaaio?a aoei coiiaeaia ?o caeaoi?noth ?iaeoeoaaoe aiiioe/io caaeaaeue
ee?oei e?i?? L1210.

Iaiao?aeii a?aecia/eoe, ui aeni?an?y aeoeaii?, oinoi?eeueiaaii? oi?ie
a?eea Smad2 niaoeeo?/ii ?iaeoeo?oueny i?ae ae??th OO?1 ye o
aaouee?anueeeo ee?oeiao e?i?? L1210, oae ? a ?acenoaioieo aei
oeenieaoeio ee?oeiao noae?i?? L1210/R (?en. 4). I?e ae?? oeenieaoeio ?
VAA-1 oinoi?eeueiaaia oi?ia a?eea Smad2 ia aeyaey?oueny, ui na?ae/eoue
i?i aenieo niaoeeo?/i?noue ?iaeoeoe?? ?aaoeyoi?iiai neaiaeo OO?.

sse aeaeii c ?en. 4, ??aaiue aeni?an?? a?eea Smad7 o ee?oeiao e?i??
L1210 ? a ?o iio?aeieo c i?aeaeuaiith ?acenoaioi?noth aei oeenieaoeio ?
iaeiaeiaei. Iaeiae, ??aaiue aeni?an?? a?eea Smad6 ? aeuei o ee?oeiao
noae?i?? L1210/R, i?ae o aaouee?anueeeo ee?oeiao oe??? e?i??.

Ine?eueee i?ae aieeaii OO?1 ye ia ee?oeie e?i?? L1210, oae ? ia ee?oeie
noae?i?? L1210/R aeyaey?oueny oinoi?eeueiaaiee a?eie Smad2, iiaeia
c?iaeoe aeniiaie, ui ?aoeaioi? ? oeio OO? ana ae i?enooi?e o iaia?aiao
ee?oei noae?i?? L1210/R, aea o cia/ii iaio?e e?eueeino?, i?ae o
aaouee?anueeeo ee?oeiao. Iiaeia i?eionoeoe, ui i?aeaeuaia
?acenoaioi?noue ee?oei noae?i?? L1210/R aei ae?? OO? ? iane?aeeii
cia/iiai cieaeaiiy a ieo e?eueeino? ?aoeaioi?a ? oeio aeaiiai oeeoie?ia.
E??i oeueiai, io?eiai? iaie ?acoeueoaoe ?ice?eaathoue ua iaeei iiaeeeaee
iaoai?ci ?acenoaioiino? ee?oei noae?i?? L1210/R aei ae?? OO?, a naia
/a?ac iineeaiiy aeni?an?? ?ia?a?oi?iiai a?eea Smad6.

?en. 4

Aeni?an?y a?ee?a Smad2, Smad3, Smad4, Smad6, Smad7 ? oinoi?eeueiaaiiai
a?eea Smad2 (Smad2 (?)) o ee?oeiao e?i?? L1210 (1-4) oa noae?i?? L1210/R
(5-8) i?ae ae??th: oeenieaoeio (2,6), OO?1 (3,7), VAA-1 (4,8). 1,5 –
iaia?iaeai? ee?oeie.

Ci?ia i?iaeoeoe?? ee?oeiaie OO? iiaea aieeaaoe ia ?icaeoie ceiye?niino?
iooeei [Terzaghi-Howe, 1989; Oeeue/aieia e ae?., 1994]. Ie anoaiiaeee,
ui ??aaiue OO?1 o eoeueoo?aeueiiio na?aaeiaeu?, eiiaeeoe?iiiaaiiio
ee?oeiaie noae?i?? L1210/R, ? cia/ii aeuee, i?ae o na?aaeiaeu?,
eiiaeeoe?iiiaaiiio aaouee?anueeeie ee?oeiaie oe??? e?i?? (?en. 5).
Oeenieaoei ?, iniaeeai, VAA-1 cia/ii i?aeaeuothoue i?iaeoeoe?th OO?1
ee?oeiaie e?i?? L1210, oiae? ye aoaeo oeeo ?a/iaei ia ee?oeie noae?i??
L1210/R ae?aaeaiee neaaoa. Ioaea, io?eiai? iaie aeai? aeacothoue ia
iiaeeea?noue ?nioaaiiy iaaiiai aca?iica’yceo i?ae ae??th ie?aieo
i?ioeiooeeiieo i?aia?ao?a ? aeni?an??th OO?1 a i?aai?ci?.

?en. 5

I?iaeoeoe?y OO?1 ee?oeiaie e?i?? L1210 (1,3,5) oa noae?i?? L1210/R
(2,4,6): 1,2 – eiio?ieue; 3,4 – i?e ae?? oeenieaoeio (0,1 iea/ie aeey
ee?oei e?i?? L1210 oa 10 iea/ie aeey ee?oei noae?i?? L1210/R); 5,6 – i?e
ae?? VAA-1 (1 ia/ie).

Aieea eaeoei?a ia ??no ee?oei e?i?? L1210 c ??ciith /ooeea?noth aei ae??
oeenieaoeio

Eaeoeie ? iie?aaeaioieie e?aaiaeaie, ye? i?eeiathoue o/anoue o
i?aeee?oeiieo aca?iiae?yo [Eooeee e ae?., 1981]. Aeaye? eaeoeie ?
iaaecae/aeii oiene/ieie aeey ee?oei ? iiaeooue aeei?enoiaoaaoeny o
i?ioeiooeeii?e oa?ai?? [Carlini and Guimaraes, 1991; Bussing, et al.,
1997]. Oiio aoei oe?eaai anoaiiaeoe, /e ia noi?iaiaeaeo?oueny iiyaa
?acenoaioiino? ee?oei e?i?? L1210 aei oeenieaoeio ci?iith ?o /ooeeaino?
aei ae?? ??cieo eaeoei?a.

I?e aeine?aeaeaii? aieeao oaeiai oe?ieiaaeeaaiiai eaeoeio, ye
eiieaiaaae?i A (Con A) anoaiiaeaii, ui eeoa aenie? eiai eiioeaio?aoe??
(1-100 iea/ie) aieiae?thoue ??no?ia?aoth/ith aeoeai?noth ?
oeeoioiene/iei aoaeoii uiaei ee?oei e?i?? L1210. Ee?oeie noae?i??
L1210/R, ?acenoaioi? aei oeenieaoeio, ? /ooeea?oeie aei aieeao Con A.
Oae, 50%-ia ?ia?aoaaiiy ?inoo ee?oei e?i?? L1210 niinoa??aa?oueny i?e
eiioeaio?aoe?? Con A 20 iea/ie, a ee?oei noae?i?? L1210/R – i?e
eiioeaio?aoe?? oeueiai eaeoeio 2 iea/ie.

Oae? oiene/i? eaeoeie, ye aaethoei?i ?eoeeie (RCA-120) ? VAA-1 neeueii
?ia?aothoue ??no ee?oei e?i?? L1210 c ??ciith /ooeea?noth aei ae??
oeenieaoeio. RCA-120 aeyaey? iaeiaeiaee ??no?ia?aoth/ee aieea ia ee?oeie
e?i?? L1210 ? noae?i?? L1210/R. I?e eiioeaio?aoe?? oeueiai eaeoeio 10
ia/ie ??no ee?oei ?ia?ao?oueny ia 80%. Iaeiae, oiene/iee aoaeo RCA-120
neeuei?oa ae?aaeaiee uiaei ee?oei noae?i?? L1210/R. Oae, i?e
eiioeaio?aoe?? aeaiiai eaeoeio 10 ia/ie na?aae ee?oei e?i?? L1210,
?acenoaioieo aei oeenieaoeio, aeyaey?oueny aeecueei 30% ia?oaeo, oiae?
ye na?aae /ooeeaeo aei ae?? oeueiai i?aia?aoo ee?oei aeaii? e?i??
a?aenioie caaeaeeo ia ia?aaeuo? 15%.

VAA-1 oaeiae cae?enith? neeueiee ??no?ia?aoth/ee ? oeeoioiene/iee aieea
ia ee?oeie e?i?? L1210 c ??ciith /ooeea?noth aei ae?? oeenieaoeio.
50%-ia ?ia?aoaaiiy ?inoo ee?oei noae?i?? L1210/R niinoa??aa?oueny i?e
eiioeaio?aoe?? VAA-1 1 ia/ie, a aaouee?anueeeo ee?oei oe??? e?i?? – i?e
eiioeaio?aoe?? eaeoeio 5 ia/ie (?en. 6a). E?euee?noue ia?oaeo ee?oei i?e
oaeeo eiioeaio?aoe?yo eaeoeio noaiiaeoue 15% a?ae caaaeueii? ?o
e?eueeino? (?en. 6a).

?en. 6

Aieea VAA-1 ia i?ie?oa?aoe?th ee?oei e?i?? L1210 oa noae?i?? L1210/R: a
– e?euee?noue aeeaeo ee?oei; a – a?aenioie ia?oaeo ee?oei ; – ee?oeie
e?i?? L1210; – ee?oeie noae?i?? L1210/R; E – eiio?ieue.

Aeey ii??aiyiiy ie oaeiae aea/eee aieea VAA-1 ia i?ie?oa?aoe?th
inaaaeiii?iaeueieo o?a?iaeano?a c aia??iia ieo? e?i?? NIH-3T3. A iaeiiio
aenia?eiaio? aeine?aeaeoaaee aieea VAA-1 ia ee?oeie e?i?? NIH-3T3, ye?
aeoeaii i?ie?oa?oaaee. A ae?oaiio eaeoeiii ia?iaeyee ee?oeie, ye?
ia?aaoaaee o noai? niieith (oaca ee?oeiiiai oeeeeo G0), aeeeeeaiiio
eiioaeoiei ?ia?aoaaiiyi ?inoo. VAA-1 aoaeoeaii ?ia?ao? ??no ee?oei e?i??
NIH-3T3. 50%-ia ?ia?aoaaiiy ?inoo niinoa??aa?oueny i?e eiioeaio?aoe??
eaeoeio 2 ia/ie. VAA-1 o eiioeaio?aoe?? aei 100 ia/ie iii?oii ia aieeaa?
ia ee?oeie, ye? ia?aaoaathoue o noai? niieith, ? eeoa i?e eiioeaio?aoe??
1 iea/ie cieaeo? ?o e?euee?noue. I?ae?aooiie ia?oaeo ee?oei iieacaa, ui
aaethoei?i 1 c iiaee, iaa?oue o eiioeaio?aoe?? 100 ia/ie ia aeeeeea?
nooo?aiai ca?eueoaiiy ?o e?eueeino?. Eeoa i?e eiioeaio?aoe?? VAA-1 1
iea/ie e?euee?noue ia?oaeo na?aae ee?oei, ye? aeoeaii i?ie?oa?othoue,
c?inoa? aei 30%, a na?aae ee?oei, ye? ia?aaoaathoue o noai? niieith –
aei 19%.

Con A, ye ? o aeiaaeeo ee?oei e?i?? L1210, aeyaey? ??no?ia?aoth/ee aieea
ia ee?oeie e?i?? NIH-3T3 eeoa o aenieeo eiioeaio?aoe?yo. Oae, o
eiioeaio?aoe?? 1 iea/ie a?i ?ia?ao? ??no ee?oei oe??? e?i?? ia 40%.
Neeueiith oeeoioiene/iith ae??th Con A aieiae?? eeoa o eiioeaio?aoe??
100 iea/ie, eiee oa?aoaaiiy o?eiaiiaei nei?i aeyaey? aeecueei 50%
ia?oaeo ee?oei.

Io?eiai? aeai? na?ae/aoue, ui ceiye?ni? ee?oeie iathoue aeuo /ooeea?noue
aei oeeoioiene/ii? ae?? VAA-1, i?ae ii?iaeuei? ee?oeie. E??i oeueiai,
/ooeea?noue aei aeaiiai eaeoeio caeaaeeoue a?ae oaeaeeino? i?ie?oa?aoe??
ee?oei-i?oaiae. Ee?oeie, ye? ?ioaineai?oa ae?eyoueny, i/aaeaeii, ?
/ooeea?oeie aei ae?? oeueiai eaeoeio.

Uia c’ynoaaoe iiaeeeaee iaoai?ci oeeoioiene/ii? ae?? eaeoei?a ia ee?oeie
e?i?? L1210 c ??ciith /ooeea?noth aei oeenieaoeio ie aeine?aeeee ?o
caeaoi?noue ?iaeoeoaaoe aiiioic. Aeyaeeiny, ui VAA-1 ? RCA-120 o
eiioeaio?aoe?? 10 ia/ie ?iaeoeothoue iiyao ?ioaineaii? o?aaiaioaoe??
AeIE, oa?aeoa?ii? aeey aiiioico, ye o ee?oeiao e?i?? L1210, oae ? a
ee?oeiao noae?i?? L1210/R (?en. 7). ConA o eiioeaio?aoe?? 1 iea/ie ia
aeeeeea? oaeiai aoaeoo. Iiyaa aiiioe/ieo o?aaiaio?a AeIE o ee?oeiao
e?i?? L1210 oa noae?i?? L1210/R niinoa??aa?oueny eeoa i?ney ?o ia?iaee
NinA o eiioeaio?aoe?? 25 iea/ie (?en. 7).

?en. 7

Aeaeo?ioi?aa?aia AeIE ee?oei e?i?? L1210 (1-5) oa noae?i?? L1210/R
(6-10), ?ieoaiaaieo i?ioyaii 48 aiae o i?enooiino?: 2,7 – RCA-120 (10
ia/ie); 3,8 – VAA-1 (10 ia/ie); 4,9 – Con A (1 iea/ie); 5,10 – Con A (25
iea/ie). 1,6 – eiio?ieue, 11 – ia?ea?e iieaeoey?ii? iane o?aaiaio?a
AeIE.

Aa?oi a?aecia/eoe, ui o inaaaeiii?iaeueieo o?a?iaeano?a c aia??iia ieo?
e?i?? NIH-3T3 VAA-1 oa RCA-120 ia ?iaeoeothoue aiiioico a
eiioeaio?aoe?yo, ye? aeeeeeathoue caaeaaeue ee?oei e?i?? L1210. Iaa?oue
i?ney ia?iaee ee?oei e?i?? NIH-3T3 aaethoei?iii 1 c iiaee o
eiioeaio?aoe?? 10 iea/ie ia niinoa??aa?oueny iiyaa oa?aeoa?ii? aeey
aiiioico o?aaiaioaoe?? AeIE.

Ii??aiyeueia aea/aiiy ae?eiceeueieo aeaoa?i?iaio iiaa?oi? ee?oei e?i??
L1210 c ??ciith /ooeea?noth aei ae?? oeenieaoeio

A?aoiaoth/e aeai? i?i aieea ie?aieo eaeoei?a ia ee?oeie e?i?? L1210 c
??ciith /ooeea?noth aei ae?? oeenieaoeio, caeiiii??ii aoei ii??aiyoe
ae?eiceeuei? aeaoa?i?iaioe iiaa?oi? oeeo ee?oei. Aei oeueiai ian
niiioeaee oaeiae niinoa?aaeaiiy i?i a?aei?ie o ?o oeeoiii?oieia?? oa
aaeaaceaiino?.

Aeey aeine?aeaeaiue aoaeaaiaeieo aeaoa?i?iaio iiaa?oi? ee?oei ie
aeei?enoaee eaeoeie, ui neoaoaaee nai???aeieie iieaeoey?ieie “ciiaeaie”
aei iaaieo aoaeaaiaeieo no?oeoo?. Ae?eii?ioa?ie iaia?ai ee?oei e?i??
L1210 oa noae?i?? L1210/R aeyaeyee i?ney ia?aiino aeaeo?ioi?aoe/ii
?icae?eaieo a?ee?a ia i?o?ioeaetheicio iaia?aio, aeei?enoiaoth/e
eaeoeie, i?/ai? ia?ieneaeacith o?iio. Aeey aeine?aeaeaiiy
aeei?enoiaoaaee oae? eaeoeie, ye Con A, PNA, eaeoei c aeiia?aaeiiai
neeiaea (HPA).

Aeyaeaii cia/i? a?aei?iiino? o neeaae? iaia?aiieo ae?eii?ioa?i?a ee?oei
e?i?? L1210 c ??ciith /ooeea?noth aei ae?? oeenieaoeio. Iae/?oe?oith c
ieo ? iineeaia aeni?an?y iaia?aiiiai ae?eii?ioa?ia i.i. 240 eAea o
ee?oeiao noae?i?? L1210/R. O aaouee?anueeeo ee?oeiao e?i?? L1210 oeae
a?eie i?aeoe/ii ia aeyaey?oueny. Aeaiee ae?eii?ioa?i aca?iiae?? ye c
PNA, oae ? c Con A, ui na?ae/eoue i?i oa, ui o eiai neeaae? i?noyoueny
ye I- oae ? N- ca’ycai? ie?ainaoa?eaei? eaioethae. Aeua iieaeoey?ia iana
oa iayai?noue I-ae?eai?a a?ae??ciy? oeae ae?eii?ioa?i a?ae
P-ae?eii?ioa?io i.i. 170 eAea, yeee aaaaea?oueny a?aeiia?aeaeueiei ca
iiyao ?acenoaioiino? ceiye?nieo ee?oei aei ae?? ??cieo e?ea?nueeeo
i?aia?ao?a (MDR-?acenoaioi?noue) [Ling, 1997].

Aieea a?ia?oa?i?? ia ee?oeie e?i?? L1210 c ??ciith /ooeea?noth aei ae??
oeenieaoeio

A iieieia?/i?e i?aeoeoe?, e??i o?i?ioa?ai??, /anoi canoiniaothoue
o?ce/i? /eiieee, oae? ye eaca?ia oa ?aioaai?anueea aei?ii?ithaaiiy, a
oaeiae a?ia?oa?i?th. Ie ii??aiyee /ooeea?noue ee?oei e?i?? L1210 oa
noae?i?? L1210/R aei ae?? oaieiaiai oieo. Aoei aeine?aeaeaii aieea
??cieo ?aaeei?a a?ia?oa?i?? ia aeeoo?caeaoi?noue oeeo ee?oei. A oe?eiio,
ee?oeie noae?i?? L1210/R, ye? ? no?ee?oeie aei oeeoioiene/ii? ae??
oeenieaoeio, ? /ooeea?oeie aei oaieiaiai oieo. Iae/?oe?oa ??cieoey i?ae
ee?oeiaie e?i?? L1210 c ??ciith /ooeea?noth aei ae?? oeenieaoeio
niinoa??aa?oueny i?e ?o i?ia??aaii? i?ioyaii 30 oa i?e 42 0N. Oaea
ia?iaea coieiy? ??no ee?oei noae?i?? L1210/R (?en. 8a), iaeiae nooo?ai
ia aieeaa? ia i?ie?oa?aoe?th aaouee?anueeeo ee?oei (?en. 8a).

?en. 8

Aieea oaieiaiai oieo (42 0N, 30 oa) ia ??no ee?oei e?i?? L1210 (a) oa
noae?i?? L1210/R (a) : – eiio?ieue; – ia?iaeai? ee?oeie.

Aeey oiai, uia a?aeiia?noe ia ieoaiiy i?i oa, yeei iiaea aooe iaoai?ci
aieeao a?ia?oa?i?? ia ee?oeie e?i?? L1210, ie aeine?aeeee o?aaiaioaoe?th
AeIE o oeeo ee?oeiao i?ney oaiia?aoo?ii? ia?iaee. Anoaiiaeaii, ui
i?ia??aaiiy i?ioyaii 30 oa i?e 42 0N aeeeeea? aiiioe/io o?aaiaioaoe?th
AeIE ye o ee?oeiao e?i?? L1210, oae ? a ee?oeiao noae?i?? L1210/R.
Iaeiae, iaiao?aeii cacia/eoe, ui e?euee?noue o?aaiaioiaaii? AeIE ?
cia/ii a?eueoith o aeiaaeeo ee?oei noae?i?? L1210/R.

Ie oaeiae aeine?aeeee ?iaeoeoe?th aiiioico a ee?oeiao e?i?? L1210 i?e
ni?euei?e ae?? a?ia?oa?i?? oa oeenieaoeio. Eiioeaio?aoe?? oeenieaoeio,
yeeie ia?iaeyee ee?oeie e?i?? L1210 oa noae?i?? L1210/R aoee,
a?aeiia?aeii, 0,05 ? 5,0 iea/ie. Anoaiiaeaii, ui ia?iaea oeenieaoeiii
aai a?ia?oa?i??th ?iaeoeo? i?eaeecii iaeiaeiaee ??aaiue aiiioico a
ee?oeiao e?i?? L1210. I?e aeiaeaaaii? i?aia?aoo /a?ac 18 aiae i?ney
i?eieiaiiy i?ia??aaiiy aiiioe/iee aoaeo iaio /eiiee?a ia ee?oeie e?i??
L1210 ? aaeaeeoeaiei. ?io? ?acoeueoaoe io?eiai? i?e ia?iaoe? ee?oei
noae?i?? L1210/R, ?acenoaioieo aei ae?? oeenieaoeio. A?ia?oa?i?y (42 0N,
30 oa) ?iaeoeo? a ieo neeueio o?aaiaioaoe?th AeIE, a ianooiia
aeiaeaaaiiy oeenieaoeio neaai aieeaa? ia oeae aoaeo. Ioaea, a?ia?oa?i?y
aeeeeea? aiiioe/io caaeaaeue ee?oei e?i?? L1210 c ??ciith /ooeea?noth
aei oeenieaoeio, i?e/iio ee?oeie noae?i?? L1210/R ? a?eueo /ooeeaeie aei
ae?? oaieiaiai oieo, i?ae aaouee?anuee? ee?oeie oe??? e?i??.

Ioaea, ?icaeoie ?acenoaioiino? ee?oei e?i?? L1210 aei i?ioeiooeeiiiai
i?aia?aoo oeenieaoeio noi?iaiaeaeo?oueny ao?aoith ?o /ooeeaino? aei
??no?ia?aoth/i? ae?? oa ?iaeoeoe?? aiiioico i?ae aieeaii OO?. I?e/eiaie
oeueiai iiaeooue aooe ii?ooaiiy aeni?an?? eiiiiiaio?a neaiaeueiiai oeyoo
OO?, a naia cieaeaiiy aeni?an?? ?aoeaioi?a ? oeio OO? oa i?aeaeuaiiy
aeni?an?? a?eea Smad6, yeee ?ia?ao? ia?aaea/o ?aaoeyoi?iiai neaiaeo
aeaiiai oeeoie?ia. Ee?oeie noae?i?? L1210/R a?ae??ciythoueny a?ae
aaouee?anueeeo ee?oei e?i?? L1210 neeaaeii ae?eii?ioa?i?a ee?oeiieo
iaia?ai, oa?aeoa?ecothoueny i?aeaeuaiei ??aiai i?iaeoeoe?? OO?1,
a?eueoith /ooeea?noth aei a?ia?oa?i??. E??i oeueiai, ee?oeie noae?i??
L1210/R, ?acenoaioi? aei oeenieaoeio, caa??aathoue /ooeea?noue aei
oeeoioiene/ii? ae?? aeayeeo ?ineeiieo eaeoei?a, cie?aia aaethoei?io 1 c
iiaee. Io?eiai? aeai? iiaeooue aooe aeei?enoai? aeey ?ic?iaee iiaeo
i?aeoiae?a o e?eoaaii? oai?eo, ye? iathoue iooeeie c i?aeaeuaiith
no?ee?noth aei ae?? oeenieaoeio.

AENIIAEE

1. I?aeaeuaia no?ee?noue aei ae?? i?ioeiooeeiiiai i?aia?aoo oeenieaoeio
ee?oei e?i?? L1210 eaeeai?? ieo? ni?aiaaea? c ?o ?acenoaioi?noth aei
?ia?aoaaiiy ?inoo oa ?iaeoeoe?? aiiioico i?ae aieeaii o?ainoi?ioth/iai
oaeoi?a ?inoo oeio (OO?).

2. Ee?oeie e?i?? L1210 eaeeai?? ieo? c i?aeaeuaiith no?ee?noth aei ae??
oeenieaoeio iathoue ci?iaio aeni?an?th eiiiiiaio?a neaiaeueiiai oeyoo
OO? ii??aiyii c aaouee?anueeeie ee?oeiaie oe??? e?i??. Oae, ?aoeaioi? ?
oeio OO?, yeee aeia?a aeni?ano?oueny a ee?oeiao e?i?? L1210, iaeaea ia
aeyaey?oueny o iaia?aii?e o?aeoe?? ee?oei noae?i?? L1210/R. O ee?oeiao
noae?i?? L1210/R niinoa??aa?oueny i?aeaeuaia aeni?an?y a?eea Smad6, yeee
? ?ia?a?oi?ii ia?aaea/? ?aaoeyoi?iiai neaiaeo OO?.

3. Ee?oeie noae?i?? L1210/R, ?acenoaioi? aei ae?? OO?1, iathoue
caeaoi?noue aei i?aeaeuaii? i?iaeoeoe?? oeueiai oeeoie?ia. Oeenieaoei oa
aaethoei?i 1 c iiaee (VAA-1) aeeeeeathoue c?inoaiiy i?iaeoeoe?? OO?1
ee?oeiaie e?i?? L1210, ? oeae aoaeo neeuei?oa ae?aaeaiee o ee?oei
aaouee?anueei? e?i??. Io?eiai? aeai? aeicaieythoue i?eioneaoe ?ieue OO?
ye iina?aaeieea o ae?? oeenieaoeio oa VAA-1 ia ee?oeie e?i?? L1210
eaeeai?? ieo?.

4. ?acenoaioi?noue aei ae?? oeenieaoeio o ee?oei e?i?? L1210
noi?iaiaeaeo?oueny ci?iaie o neeaae? ?o iaia?aiieo ae?eii?ioa?i?a.
Iaea?eueo /?oei ae?aaeaiith a?aei?ii?noth i?ae aaouee?anueeeie ee?oeiaie
e?i?? L1210 ? ee?oeiaie noae?i?? L1210/R ? i?aeaeuaia aeni?an?y a
inoaii?o iaia?aiiiai ae?eii?ioa?ia i.i. 240 eAe.

5. Ee?oeie e?i?? L1210 c i?aeaeuaiith ?acenoaioi?noth aei oeenieaoeio
caa??aathoue /ooeea?noue aei ae?? ie?aieo oeeoioiene/ieo eaeoei?a,
cie?aia – VAA-1.

6. Ae?y VAA-1 ia ee?oeie e?i?? L1210 i?ecaiaeeoue aei ?o aiiioe/ii?
caaeaae?, oiae? ye o inaaaeiii?iaeueieo o?a?iaeano?a c aia??iia ieo?
e?i?? NIH-3T3 VAA-1 ?ia?ao? ??no, aea ia aeeeeea? caaeaae? ee?oei.

7. Ee?oeie e?i?? L1210, ye? aieiae?thoue i?aeaeuaiith no?ee?noth aei
ae?? oeenieaoeio, ? /ooeea?oeie aei a?ia?oa?i??, i?ae aaouee?anuee?
ee?oeie oe??? e?i??. A?ia?oa?i?y aeeeeea? aiiioe/io caaeaaeue ee?oei
e?i?? L1210.

8. Aeyaeai? o ?iaio? a?aei?iiino? i?ae eaeeai?/ieie ee?oeiaie e?i??
L1210, no?eeeie aei ae?? oeenieaoeio, oa ?o aaouee?anueeeie
iiia?aaeieeaie uiaei /ooeeaino? aei ?ia?a?oi?iiai oeeoie?ia OO?1,
ie?aieo ?ineeiieo eaeoei?a oa a?ia?oa?i?? iiaeooue aooe
aenia?eiaioaeueiei i?aea?oioyi o ?ic?iaoe? iiaeo i?aeoiae?a aeey
iiaeieaiiy iaaooi? ?acenoaioiino? ceiye?nieo ee?oei aei oeueiai
i?ioeiooeeiiiai i?aia?aoo.

NIENIE I?AOeUe, IIOAE?EIAAIEO CA OAIITH AeENA?OAOe??

1. Stoika R.S., Yakymovych M.Ya., Yakymovych I.A., Chekhun V.F. Murine
L1210 leukemia cells resistant to cis-diaminedichloroplatinum (II)
action are also refractory to transforming growth factor 1-induced
growth inhibition // Yenia?eiaioaeueiay iieieiaey. – 1998. – O. 20. –
?3-4. – N. 256-258.

2. Stasyk T.V., Antonyuk V.A., Yakymovych M.Ya., Yakymovych I.A., Yanish
Yu.V., Shishova Yu.V., Shliakhovenko V.A., Chekhun V.F., Stoika R.S.,
Lutsik-Kordovsky M.D. A comparative study of cell surface glycosyl
determinants in sensitive and resistant to cisplatin L1210 murine
leukemia cells // Yenia?eiaioaeueiay iieieiaey. – 1998. – O. 20. – ?3-4.
– N. 204-209.

3. Yakymovych M.Ya., Yakymovych I.A., Tryndiak V.P., Stoika R.S.
Hyperthermia induces apoptosis in cisplatin-resistant murine L1210
leukemia cells // Yenia?eiaioaeueiay iieieiaey. – 1999. – O. 21. – ?2. –
N. 154-156.

4. Stoika R.S., Yakymovych M.Y., Yakymovych I.A., Chekhun V.F.
Resistance to cis-diaminedichloroplatinum (II) in murine L1210 leukemia
cells is accompanied by their resistance to transforming growth factor
1-induced growth inhibition and apoptosis // Anti-Cancer Drugs. – 1999.
– V. 10. – ?5. – ?. 457-463.

5. Yakymovych M., Yakymovych I., Antonyuk V., Lutsik-Kordovsky M.,
Stoika R. Lectins’ cytotoxicity for L1210 murine leukemia cells with
different sensitivity to anticancer drug cisplatin // Aenia?eiaioaeueia
oa ee?i?/ia o?c?ieia?y ? a?io?i?y. – 1999. – ?2. – N. 39-45.

6. Stoika R.S., Yakymovych M.Y., Yakymovych I.A. Cross-resistance to
cisplatin and transforming growth factor beta 1 in murine L1210 leukemia
cells // 6th European Society for Analytical Cellular Pathology
Congress. – Heidelberg (Germany). – Analytical Cellular Pathology. –
1999. – V. 18. – ?1. – P. 49.

7. Lutsik-Kordovsky M.D., Antonyuk V.A., Stasyk T.V., Yakymovych M.Ya.,
Yakymovych I.A., Hellman U., Soushelnitsky S., Stoika R.S., Lutsyk A.D.
Hemagglutinating lectin from fruit bodies of Amanita phalloides:
isolation, properties and biological activity // Abstracts of papers
presented at INTERLEC 18. – University of Portsmouth. – 1999. – P. 77.

sseeiiae/ I.ss. Aieea o?ainoi?ioth/iai oaeoi?a ?inoo oeio ia ee?oeie
e?i?? L1210 eaeeai?? ieo? c ??ciith /ooeea?noth aei ae?? oeenieaoeio. –
?oeiien.

Aeena?oaoe?y ia caeiaoooy iaoeiaiai nooiaiy eaiaeeaeaoa a?ieia?/ieo iaoe
ca niaoe?aeuei?noth 03.00.04 – a?io?i?y. – ?inoeooo a?io?i?? ?i. I.A.
Iaeeaae?ia IAI Oe?a?ie, Ee?a, 1999.

Aeena?oaoe?th i?enay/aii aea/aiith iaoai?ci?a iaaooi? ?acenoaioiino?
ceiye?nieo ee?oei e?i?? L1210 eaeeai?? ieo? aei ae?? i?ioeiooeeiiiai
i?aia?aoo oeenieaoeio. Anoaiiaeaii, ui ee?oeie oe??? e?i??, ye?
i?iyaeythoue i?aeaeuaio no?ee?noue aei ae?? oeenieaoeio, ? ?acenoaioieie
aei aieeao o?ainoi?ioth/iai oaeoi?a ?inoo oeio (OO?). OO? i?eai?/o?
??no ? ?iaeoeo? aiiioic o ee?oeiao e?i?? L1210, aea ia a ee?oeiao
noae?i??, ?acenoaioieo aei ae?? oeenieaoeio. I?e/eiaie no?eeino? aei
aieeao OO? iiaeooue aooe cieaeaia aeni?an?y a ee?oeiao aeaii? noae?i??
?aoeaioi?a ? oeio OO? oa i?aeaeuaia aeni?an?y a?eea Smad6 –
aioo??oiueiee?oeiiiai ?ia?a?oi?a ia?aaea/? neaiaeo oeueiai oeeoie?ia.
Iiyaa ?acenoaioiino? ee?oei e?i?? L1210 aei ae?? oeenieaoeio
noi?iaiaeaeo?oueny ci?iaie o neeaae? ae?eii?ioa?i?a ee?oeiieo iaia?ai,
i?aeaeuaiiyi /ooeeaino? ee?oei aei a?ia?oa?i??, a oaeiae i?aeaeuaiith
i?iaeoeoe??th OO?1. Ee?oeie e?i?? L1210 c i?aeaeuaiith ?acenoaioi?noth
aei oeenieaoeio caa??aathoue /ooeea?noue aei ae?? aeayeeo ?ineeiieo
eaeoei?a, cie?aia – aaethoei?io 1 c iiaee.

Eeth/ia? neiaa: OO?, oeenieaoei, eaeeai?y, ?acenoaioi?noue, aiiioic,
?ia?aoaaiiy ?inoo, eaeoeie, a?ia?oa?i?y.

Yakymovych M.Ya. Effect of transforming growth factor type on L1210
murine leukemia cells differing in their sensitivity to cisplatin
action. – Manuscript.

Thesis for a scientific degree of candidate of biological sciences by
speciality 03.00.04 – biochemistry. – O.V. Palladin Institute of
Biochemistry of the National Academy of Sciences of Ukraine, Kyiv, 1999.

The thesis is related to study of the mechanisms of acquired resistance
of malignant L1210 murine leukemia cells to the action of antitumor drug
cisplatin. It was found that the cells of this line which show an
increased resistance to cisplatin action, were also resistant to the
action of transforming growth factor (TGF). TGF1 inhibited growth and
induced apoptosis in the L1210 cells, but not in the cells of subline
resistant to cisplatin action. The reasons for such effects of TGF1
could be in decreased expression of type I receptor of TGF and increased
expression of the intracellular protein Smad6 which inhibiting TGF
signal transduction. The appearance of resistance to cisplatin in the
L1210 cells was accompanied by changes in the composition of membrane
glycoproteins, increased sensitivity to hyperthermia as well as by the
increased cellular production of TGF1. The L1210 cells resistant to
cisplatin retain sensitivity to cytotoxic action of some lectins, e.g.
Viscum album agglutinin-1.

Key words: TGF, cisplatin, leukemia, resistance, apoptosis, growth
inhibition, lectins, hyperthermia.

sseeiiae/ I.ss. Aeeyiea o?ainoi?ie?othuaai oaeoi?a ?inoa oeia ia eeaoee
eeiee L1210 eaeeaiee iuoe n ?aciie /oanoaeoaeueiinoueth e aeaenoaeth
oeenieaoeia.- ?oeiienue.

Aeenna?oaoeey ia nieneaiea o/aiie noaiaie eaiaeeaeaoa aeieiae/aneeo iaoe
ii niaoeeaeueiinoe 03.00.04 – aeioeiey. – Einoeooo aeioeiee ei. A.A.
Iaeeaaeeia IAI Oe?aeiu, Eeaa, 1999.

Aeenna?oaoeey iinayuaia eco/aieth iaoaieciia i?eia?aoaiiie
?acenoaioiinoe ceiea/anoaaiiuo eeaoie eeiee L1210 eaeeaiee iuoe e
aeaenoaeth i?ioeaiiiooieaaiai i?aia?aoa oeenieaoeia.

A ea/anoaa iauaeoa enneaaeiaaiee eniieueciaaee eeaoee eeiee L1210
eaeeaiee iuoe e eeaoee yoie aea eeiee, eioi?ua oa?aeoa?eciaaeenue
iiauoaiiie ?acenoaioiinoueth e aeaenoaeth i?ioeaiiiooieaaiai i?aia?aoa
oeenieaoeia (noaeeiey L1210/R).

N oeaeueth eco/aiey aiciiaeiiai iaoaiecia ?acenoaioiinoe eeaoie
noaeeiee L1210/R e aeaenoaeth oeenieaoeia n?aaieee /oanoaeoaeueiinoue
yoeo eeaoie e eo ?iaeeoaeueneeo i?aaeoanoaaiieeia e aeeyieth
o?ainoi?ie?othuaai oaeoi?a ?inoa oeia (OO?). OO?1 eiaeae?oao aeeth/aiea
3I-oeieaeeia a AeIE eeaoie eeiee L1210, oaiaoaao eo i?ieeoa?aoeeth e
eieiieaia?aciaaiea a n?aaea, niaea?aeauae 0,33% aaa?a, ii ia aeeyao ia
yoe iieacaoaee a neo/aa eeaoie noaeeiee L1210/R. Oaeia aeaenoaea OO? ia
eeaoee eeiee L1210, ii-aeaeeiiio, iaoneiaeaii eiaeoeoeeae aiiioica e,
eae iieacaii, caaeneo io eiioeaio?aoeee nuai?ioee e?iae a
eoeueoo?aeueiie n?aaea. Eeaoee noaeeiee L1210/R ia/oanoaeoaeueiu e
eiaeoeoeee aiiioica iiae aeeyieai aeaiiiai oeeoieeia.

Aeey auyniaiey iaoaieciia ?acenoaioiinoe eeaoie noaeeiee L1210/R e
aeaenoaeth OO? enneaaeiaaee yeni?anneth ioaeaeueiuo eiiiiiaioia
neaiaeueiiai iooe yoiai oaeoi?a ?inoa, a eiaiii niaoeeoe/aneeo
?aoeaioi?ia ? e ?? oeia, e aaeeia Smad, eioi?ua yaeythony
aioo?eeeaoi/iuie ia?aiin/eeaie neaiaea OO?. Eeaoee eeiee L1210 n ?aciie
/oanoaeoaeueiinoueth e aeaenoaeth oeenieaoeia ?acee/athony ii o?iaith
yeni?annee ?aoeaioi?a ? oeia OO?. Yoio iaia?aiiue aaeie oi?ioi au?aaeai
a eeaoeao eeiee L1210 e i/aiue neaai auyaeyaony a eeaoeao noaeeiee
L1210/R. ?aoeaioi?u ?? oeia OO? i?enoonoaotho a iaia?aiiuo i?aia?aoao
eae ?iaeeoaeueneeo, oae e ?acenoaioiuo e aeaenoaeth oeenieaoeia eeaoie
eeiee L1210. Iaoiaeii Western-aeio aiaeeca n eniieueciaaieai
niaoeeoe/aneeo aioeoae ia iaia?oaeaii ?acee/ee a yeni?annee aaeeia
Smad2, Smad3, Smad4, Smad7 iaaeaeo ?iaeeoaeueneeie eeaoeaie eeiee L1210
e eeaoeaie noaeeiee L1210/R. A oi aea a?aiy o?iaaiue yeni?annee aaeea
Smad6, eioi?ue eiaeae?oao ia?aaea/o neaiaea OO?, iiauoai a eeaoeao,
?acenoaioiuo e aeaenoaeth oeenieaoeia. Oaeei ia?acii, aiciiaeii, /oi
?acenoaioiinoue eeaoie noaeeiee L1210/R e aeaenoaeth OO? yaeyaony
neaaenoaeai nouanoaaiiiai nieaeaiey o?iaiy yeni?annee a ieo ?aoeaioi?a ?
oeia aeaiiiai oeeoieeia e oaaee/aiey o?iaiy yeni?annee eiaeaeoi?iiai
aaeea Smad6.

Onoaiiaeaii, /oi niaea?aeaiea OO?1 a eoeueoo?aeueiie n?aaea,
eiiaeeoeeiie?iaaiiie eeaoeaie noaeeiee L1210/R, cia/eoaeueii i?aauoaao
oaeiaia a n?aaea, eiiaeeoeeiie?iaaiiie ?iaeeoaeueneeie eeaoeaie.
Oeenieaoei e aaaethoeiei 1 ec iiaeu (VAA-1) cia/eoaeueii iiauoatho
i?iaeoeoeeth OO?1 eeaoeaie eeiee L1210. Aeaenoaea aeaiiuo aauanoa ia
eeaoee noaeeiee L1210/R au?aaeaii cia/eoaeueii neaaaa. Iieo/aiiua
?acoeueoaou oeacuaatho ia aiciiaeiinoue nouanoaiaaiey ii?aaeae?iiie
acaeiinayce iaaeaeo aeaenoaeai oeenieaoeia e i?iaeoeoeeae OO?1.

?acenoaioiinoue eeaoie eeiee L1210 e aeaenoaeth oeenieaoeia
nii?iaiaeaeaaony eciaiaieyie a ninoaaa aeeeii?ioaeiia eeaoi/iuo iaia?ai.
Iaeaieaa oa?aeoa?iui ioee/eai yaeyaony iiauoaiiay yeni?anney a eeaoeao
noaeeiee L1210/R aeeeii?ioaeia i.i. 240 eAea, eioi?ue oi?ioi
acaeiiaeaenoaoao n eiieaiaaaeeiii A (Con A) e eaeoeiii a?aoena (PNA).
Aeueoay iieaeoey?iay ianna e iaee/ea I-aeeeaiia ioee/aao yoio
aeeeii?ioaei io ?-aeeeii?ioaeia, ioaaonoaaiiiai ca iiyaeaiea
onoie/eainoe eeaoie e ?acee/iui eaea?noaaiiui i?aia?aoai
(MDR-?acenoaioiinoue). A ?iaeeoaeueneeo eeaoeao eeiee L1210 aeeeii?ioaei
i.i. 240 eAea i?aeoe/anee ionoonoaoao.

Onoaiiaeaii, /oi eeaoee eeiee L1210 n iiauoaiiie ?acenoaioiinoueth e
oeenieaoeio /oanoaeoaeueiu e oeeoioiene/aneiio aeaenoaeth iaeioi?uo
eaeoeiia, a oii /enea – VAA-1. VAA-1 ieacuaaao aeeyiea ia eeaoee eeiee
L1210, eiaeooee?oy a ieo aiiioic. A oi aea a?aiy VAA-1 ia aucuaaao
aeaaee inaaaeiii?iaeueiuo oea?iaeanoia ec yia?eiia iuoe eeiee NIH-3T3,
oioy e eiaeae?oao eo ?ino. Oaeei ia?acii, iieo/aiiua ?acoeueoaou
naeaeaoaeuenoaotho i aieaa aunieie /oanoaeoaeueiinoe e aeaenoaeth VAA-1
ceiea/anoaaiiuo eeaoie ii n?aaiaieth n ii?iaeueiuie eeaoeaie.

Eeaoee eeiee L1210 n iiauoaiiie ?acenoaioiinoueth e oeenieaoeio
yaeythony aieaa /oanoaeoaeueiuie e aeaenoaeth aeia?oa?iee, /ai
?iaeeoaeueneea eeaoee aeaiiie eeiee. Eeaoee eeiee L1210 n ?aciie
/oanoaeoaeueiinoueth e oeenieaoeio ?acee/athony ii ianooaaai
aiiioe/aneie aeaaee, aucaaiiie aeia?oa?ieae.

Auyaeaiiua ?acee/ey iaaeaeo ?iaeeoaeueneeie eeaoeaie eeiee L1210
eaeeaiee iuoe e eo i?iecaiaeiuie n iiauoaiiie onoie/eainoueth e
aeaenoaeth oeenieaoeia, eanathueany eo /oanoaeoaeueiinoe e OO?,
ioaeaeueiui ?anoeoaeueiui eaeoeiai e aeia?oa?iee, iiaoo auoue iieaciuie
a auyniaiee iaoaieciia aicieeiiaaiey ?acenoaioiinoe ceiea/anoaaiiuo
eeaoie e aeaenoaeth oeenieaoeia e iicaieytho iaiaoeoue iooe ?ac?aaioee
iiauo iiaeoiaeia aeey i?aiaeieaiey oaeie ?acenoaioiinoe.

Eeth/aaua neiaa: OO?, oeenieaoei, eaeeaiey, ?acenoaioiinoue, aiiioic,
eiaeae?iaaiea ?inoa, eaeoeiu, aeia?oa?iey.

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