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

?INOEOOO AENIA?EIAIOAEUeII? IAOIEIA??, IIEIEIA?? ? ?AAe?IA?IEIA??
?I.?.?.EAAAOeUeEIAI

I?I?NOA?NOAI IOI?IIE CAeI?IA’ss OE?A?IE

OE?A?INUeEEE IAOEIAI-AeINE?AeIEE ?INOEOOO IIEIEIA?? ? ?AAe?IEIA??

CAAAEAAE* IEOAEEI IAO?IAE*

OAeE 578.245.4 : 577.151.54 : 57.085.23

NENOAIA 2-5 IE?AIAAeAI?EAOO A IOOEEIIEO OA A??ON?IO?EIAAIEO EE?OEIAO
I?E Ae?? ?IOA?OA?II?A OA ?? IIAeOEssOe?ss ?AOEII?AeAIE

14.01.07 — Iieieia?y

Aaoi?aoa?ao

aeena?oaoe?? ia caeiaoooy iaoeiaiai nooiaiy

eaiaeeaeaoa a?ieia?/ieo iaoe

EE?A-1999 ?.

Aeena?oaoe??th ? ?oeiien

?iaioa aeeiiaia a ?inoeooo? aenia?eiaioaeueii? iaoieia??,iieieia?? ?
?aae?ia?ieia?? ?i. ?.?.Eaaaoeueeiai IAI Oe?a?ie

Iaoeiaee ea??aiee

-aeaaeai?e IAI Oe?a?ie,

aeieoi? iaaee/ieo iaoe, i?ioani?

Aooaiei Ciy Aiae???aia,

caa?aeoaa/ a?aeae?eo iaoai?ci?a eaeeiciaaiaco ?inoeoooo
aenia?eiaioaeueii? iaoieia??, iieieia?? ? ?aae?ia?ieia?? ?i.
?.?.Eaaaoeueeiai IAI Oe?a?ie,

Io?oe?ei? iiiiaioe:

-aeieoi? iaaee/ieo iaoe, i?ioani?

Oeyoiaaiei Aieiaeeie? Ieaen?eiae/,

caa?aeoaa/ a?aeae?eo aiceiioa?ai?? iooeei

?inoeoooo aenia?eiaioaeueii? iaoieia??, iieieia?? ? ?aae?ia?ieia?? ?i.
?.?.Eaaaoeueeiai IAI Oe?a?ie,

-/eai-ei?aniiiaeaio IAI Oe?a?ie, aeieoi? a?ieia?/ieo iaoe, i?ioani?

Aey/aiei Iaoae?y Na?a??aia,

caa?aeoaa/ a?aeae?eo iieaeoey?ii? a?ieia?? a??on?a

?inoeoooo i?e?ia?ieia?? ? a??onieia??

?i. Ae.E.Caaieioiiai IAI Oe?a?ie,

I?ia?aeia onoaiiaa

-Ee?anueea iaaee/ia aeaaeai?y i?neyaeeieiiii? ina?oe ?i. I.E.Ooieea IIC
Oe?a?ie, eaoaae?e iieieia?? ? a??onieia??, i.Ee?a

Caoeno a?aeaoaeaoueny ‘’_____’’___________ 1999 ?. i ________ aiaeei? ia
can?aeaii? niaoe?ae?ciaaii? a/aii? ?aaee Ae 26.155.01 a ?inoeooo?
aenia?eiaioaeueii? iaoieia??, iieieia?? ? ?aae?ia?ieia?? ?i.
?.?.Eaaaoeueeiai IAI Oe?a?ie (252022, Ee?a-22, aoe. Aaneeuee?anueea, 45)

C aeena?oaoe??th iiaeia iciaeiieoenue o a?ae?ioaoe? ?AII? IAI Oe?a?ie

Aaoi?aoa?ao ?ic?neaiee ‘’______’’_______________1999 ?.

A/aiee nae?aoa?

niaoe?ae?ciaaii? A/aii? ?aaee

aeieoi? iaaee/ieo iaoe

?.A.Aa?aiaiei

CAAAEUeIA OA?AEOA?ENOEEA ?IAIOE

Aeooaeuei?noue oaie. ?ioa?oa?iie (?OI) iin?aeathoue iaeia c ia?oeo
i?noeue na?aae oeeoie?i?a, ye? aeei?enoiaothoueny a no/ani?e iaaeeoeei?.
Iayai?noue i?ioei?ie?oa?aoeaieo oa ?ioiiiiaeoeyoi?ieo aoaeo?a o ?OI
iaoiiaeea iiaeeeaino? ?o canoinoaaiiy a iieieia?/i?e i?aeoeoe?. Ee?i?/i?
aeine?aeaeaiiy, i?iaaaeai? c i?aia?aoaie ?aeiia?iaioieo ?OI, aeicaieeee
iaeiie/eoe /eiaeee aeina?ae, iaiao?aeiee aeey ?ic?iaee ?aoe?iiaeueieo
noai ?ioa?oa?iiioa?ai?? (A?oia 1996; Aiceaiia n niaao. 1998; Talpaz
1995; Kantarjian et al 1996). Canoinoaaiiy ?OI a eiiieaen? c
o?i?ii?aia?aoaie oa ?ioeie caniaaie i?ioeiooeeiii? oa?ai?? aeicaieeei
aeinyaoe cia/ieo ?acoeueoao?a a e?eoaaii? aieinaoiee?oeiiiai eaeeico
(Golomb et al 1996), o?ii?/iiai i??eieaeeico (Tura 1996) oa
iaoanoacoth/iai ?aeo ie?ee (Aiceaiia n niaao. 1997). ?acii c oei, ia
iiaeia ia cacia/eoe, ui e aei oeueiai /ano ee?i?/i? noaie aeei?enoaiiy
?OI eeoathoueny caeaa?eueoiai aii??e/ieie oa ia?iaeea?aeoae?ciaaieie,
i?e oeueiio ?nio? iaaiee ?ic?ea i?ae iia?oi?ie aeaieie i?i iieaeoey?i?
iaoai?cie ae?? ?OI oa ?nioth/eie iaa?oiooaaiiyie noai ?o canoinoaaiiy.

Ca?aeii c no/anieie oyaeaiiyie /eneaii? a?ieia?/i? aoaeoe ?OI a?aoo?
?aoo iia’ycai? c iaiaaeaiei eieii aoaeoi?ieo iaoai?ci?a nenoaie ?OI, ye?
caioneathoueny a ?acoeueoao? aca?iiae?? ?OI c ?aoeaioi?aie ia iiaa?oi?
ee?oei. Iaeia c oeaio?aeueieo i?noeue na?aae oaeeo aoaeoi?ieo eaiie
iin?aea? nenoaia 2-5 ie?aiaaeai?eaoo (2-5A), aieiaiei eiiiiiaioii yei? ?
niaoeeo?/iee oa?iaio, 2-5A neioaoaca (Kerr and Brown 1978). Naia oeueiio
oa?iaioo inoaii?i /anii i?eae?eythoue cia/io oaaao a ni?iaao ciaeoe
caaaeueiee ciaiaiiee aeey iiyniaiiy ??ciiiai?oieo aoaeo?a ?OI.
Aeyaeeinue, ui nenoaia 2-5A iia’ycaia c aeeoa?aioe?thaaiiyi ee?oei,
?aaoethaaiiyi ?o i?ie?oa?aoe?? oa iiaeoethaaiiyi ?yaeo a?ineioaoe/ieo
i?ioean?a (Player and Torrenece 1998), aiia aa?a o/anoue a i?aeo?eiaii?
ee?oeiiiai aiiainoaco oa a oaeeo ooiaeaiaioaeueieo i?ioeanao ye aiiioic
(Castelli et al 1998).

Ine?eueee ae?y ?OI ia ni?eeiyoeea? aei ieo ee?oeie a a?eueoino?
aeiaaee?a noi?iaiaeaeo?oueny ?iaeoeoe??th 2-5A neioaoace, aecia/aiiy
aeoeaiino? oeueiai oa?iaioo iiaea aooe ei?eniei ye aeey i?iaiicoaaiiy
aoaeoeaiino? canoinoaaiiy ?OI, oae ? aeey iii?oi?eiao ?ioa?oa?iiioa?ai??
(Ferbus et al 1990; Moritz et al 1992). Ci?ie aeoeaiino? 2-5A neioaoace
iiaeia aecia/aoe ia eeoa a ee?oeiao iooeei, a e a aoaeoi?ieo ee?oeiao
?ioiii? nenoaie, ui iiaea ni?eyoe ?icoi?iith aoaeo?a, ye? ?OI ni?aaey?
iiina?aaeeiaaii.

A ?iaioao inoaii?o ?ie?a, i?enay/aieo aea/aiith /eneaiieo ca’yce?a i?ae
ee?oeiaie, ye? iiina?aaeeothoueny oeeoie?iaie oa oaeoi?aie ?inoo, /eiaea
oaaaa i?eae?ey?oueny ?a/iaeiai, ye? iaeaaeaoue aei ?aoeii?ae?a,
iineeeany ?ioa?an ? aei ?o ee?i?/iiai canoinoaaiiy a iieieia?/i?e
i?aeoeoe? (Parkinson 1992; Berg 1997). Iniaeeai oe?eaaeie ? aeai?, ui
na?ae/aoue i?i iiaeeeaino? aaeeoeaieo oa neia?a?/ieo
i?ioei?ie?oa?aoeaieo aoaeo?a ?aoeii?ae?a a ii?aeiaii? c ?OI
(Giandomenico et al 1998). I?e oeueiio, ye aeyaeeinue inoaii?i /anii,
?aoeii?aee iiaeooue aieeaaoe aaciina?aaeiuei ia nenoaio 2-5A, /ei
iiaeooue oi/a a /anoeiai aooe iiyniai? iiae?ai? aoaeoe aca?iiae??
(Lancillotti et al 1995; Gianni et al 1997; Pelicano et al 1997). ?acii
c oei a oeeo ieoaiiyo ua ?nio? aaaaoi noia?a/iinoae ? ?ic?iaea
?aoe?iiaeueieo noai eiia?iiaaii? oa?ai?? c canoinoaaiiyi ?aoeii?ae?a
iio?aao? iiaeaeueoeo aeine?aeaeaiue. Aiae?c aieeao ?aoeii?ae?a ia
i?ie?oa?aoe?th ee?oei oa aca?iiae?? ?aoeii?ae?a c nenoaiith ?OI ia iiaea
i?iaiaeeoenue a?aeie?aieaii a?ae aiae?co aieeao ?aoeii?ae?a ia
?ai?iaeoeoe?th a??on?a c a?aooaaiiyi, cie?aia, aca?iicaeaaeiino? i?ae
?ao?ia??onaie oa ?iaeoeiaaieie ? niiioaiieie iooeeiaie a
aenia?eiaioaeuei?e iieieia??, a oaeiae ee?i?/iiai cia/aiiy ?ao?ia??onieo
?ioaeoe?e o ethaeeie, oei a?eueoa, ui inoaii?i /anii iaaia oaaaa
i?eae?ey?oueny iiaeeeaiio aeei?enoaiith ?aoeii?ae?a aeey oa?ai??
A?E-anioe?eiaaii? na?eiie Eaiio? oa A?E-anioe?eiaaieo e?ioii (Baily et
al 1995). Aei oiai ae an? aniaeoe, iia’ycai? c aca?iiae??th i?ae
?aoeii?aeaie oa nenoaiith ?OI, aaaeeea? ? aeey ee?i?/iiai canoinoaaiiy
?OI oa ?aoeii?ae?a a iieieia??.

Ca inoaii? aeanyoe??//y ?OI ana oe?oa canoiniaothoueny a eiia?iiaai?e
oa?ai?? nie?aeieo iooeei ??cieo eieae?caoe?e (Ai?iioeiaa 1996). *?eueia
i?noea na?aae ieo iin?aeathoue aeaye? iioe?ai? iooeeie i?aai?a
na/iaeaaaeaiiy, cie?aia ?ae ie?ee oa ?ae na/iaiai i?oo?a (Horoszewicz
and Murphy 1989; Torti and Lum 1987). Canoinoaaiiy ?OI aeueoa o oai?eo
ia ?ae na/iaiai i?oo?a aeicaiey? caiia?aaoe ?aoeeaeeaoaaiith i?ney
o??o?a?/iiai aeaeaeaiiy ia?aeiii? iooeeie. I?e oeueiio
aeei?enoiaothoueny ia?aaaae a?ae noai?aiiy eieaeueieo i?aeaeuaieo
eiioeaio?aoe?e ?OI caaaeyee iiaeeeaino? aioo??i?oo?iaiai aaaaeaiiy
i?aia?aoo (Chodak 1989). Iaeiae, iac’yniaaiei eeoa?oueny ieoaiiy, /iio a
?yae? aeiaaee?a iooeeie ? a?eueo ni?eeoyoeea? aei ?OI, a a ?ioeo
aeiaaeeao — a?aeiinii a?eueo ?acenoaioieie. Iaynii oaeiae, yeei ?
ni?aa?aeiioaiiy aaciina?aaeiueiai aieeao ?OI ia iooeeii? ee?oeie oa
iiina?aaeeiaaii? ae?? ?OI, a?aoiaoth/e cia/io ?ieue ?ioiiiai eiiiiiaioo,
a iiaeeeai ? ii?ooaiue a nenoai? ?OI, a iaoiaaiac? ?aeo na/iaiai i?oo?a.
Iane?euee? a?aeiii c e?oa?aoo?e, aeine?aeaeaiiy noaio nenoaie 2-5A a
ee?oeiao ?aeo na/iaiai i?oo?a aein? ua ia i?iaiaeeeenue. A?aeiinii
iaeiaea/aieie eeoathoueny ? i?iaeaie aca?iiae?? ?OI c ?aoeii?aeaie a
oa?ai?? ?aeo na/iaiai i?oo?a, iacaaaeath/e ia oa, ui iiae?ai? noaie
e?eoaaiiy aaea ii/aee aei?iaoaaoenue a ee?i?/i?e i?aeoeoe?.

?OI ciaeoee nai? canoinoaaiiy ? i?e e?eoaaii? iaoanoacoth/iai ?aeo
ie?ee, iniaeeai a ii?aeiaii? c oeeoinoaoeeaie oa ?ioa?eaee?iii-2 (?E-2)
(Aiceaiia n niaao. 1997; Belldegrun et al 1996; Atzpodien 1995).
Iniaeeai ia?niaeoeaieie ? i?aeoiaee c iia?e?caoe??th in vitro
e?ioioeeo?a, ye? ?io?eueo?othoue iooeeie (Finke et al 1994).
Iacaaaeath/e ia oa, ui aaea iaeiie/aii /eiaei aeaieo i?i aieea ?OI oa
?aoeii?ae?a ia aeaye? c aoaeoi?ieo ee?oei ?ioiii? nenoaie (Bonavida et
al 1993), iac’yniaaieie eeoathoueny ieoaiiy uiaei noaio nenoaie 2-5A ye
a i?e?iaeieo e?ea?ieo ee?oeiao, oae ? a e?ioioeeoao, ye? ?io?eueo?othoue
iooeeie, iniaeeai a ieai? ni?eueiiai canoinoaaiiy ?OI oa ?E-2.

Aeooaeuei?noue oaiaoeee aeine?aeaeaiue, oaeei /eiii, aecia/a?oueny
iaiao?aei?noth iaa?oiooaaiiy ?aoe?iiaeueieo noai canoinoaaiiy ?OI oa
?aoeii?ae?a a ee?i?/i?e i?aeoeoe? oa ?ic?iaee ?ioi?iaoeaieo iaoiae?a,
ye? iiaee a na?ae/eoe i?i ni?eeiyoeea?noue aei ?OI a ii?aeaii? c
iiaeeo?eaoi?aie a?ieia?/ii? a?aeiia?ae?, caaaeath/e ia aeineoue oe?iea
ee?i?/ia canoinoaaiiy ye ?OI, oae ? eiia?iiaaii? oa?ai??, yea aeeth/a?
?ioa?oa?iiioa?ai?th. A oai?aoe/iiio aniaeo? iniaeeaee ?ioa?an noaiiaeei
ieoaiiy i?i ?ieue nenoaie 2-5A ye iiaeeeai? caaaeueii? aoaeoi?ii? eaiee,
ui iaoiiaeth? ??ciiiai?oi? aoaeoe ?OI.

Iaoa ? caaea/? aeine?aeaeaiiy. Iniiaia iaoa — iaea?aeaiiy iiaeo aeaieo
i?i ooieoe?iioaaiiy eeth/iaiai oa?iaioo nenoaie ?OI, 2-5A neioaoace, a
ee?oeiao ia?auaiethaaieo e?ioiaeanoi?aeieo e?i?e, iooeeiieo ee?oeiao oa
aoaeoi?ieo ee?oeiao ?ioiii? nenoaie oai?eo ia ?ae na/iaiai i?oo?a oa ?ae
ie?ee oa aiae?c iiaeeeaino? canoinoaaiiy iaoiaeo oanooaaiiy aeoeaiino?
2-5A neioaoace aeey aecia/aiiy ni?eeiyoeeaino? ee?oei ??ciiai aaiaco aei
aeciaaiiiai ?OI, a oaeiae aiae?c iaoai?ci?a iiaeoeyoe?? aoaeo?a ?OI i?ae
ae??th ?aoeii?ae?a.

Aeey aeinyaiaiiy oe??? iaoe aoei iinoaaeaii oae? caaaeaiiy:

— i?iaiae?coaaoe i?ioea??oni? oa i?ioei?ie?oa?aoeai? aoaeoe ?OI i?e
?ioaa?aoeai?e a??oni?e ?ioaeoe??, cie?aia a ee?oeiao ia?auaiethaaieo
eoeueoo? ieoa/eo e?ioii, ye? i?iaeoeothoue aiaeiaaii? ?ao?ia??one;

— i?iaiae?coaaoe iniiai? ia?aiao?e nenoaie 2-5 A a ee?oeiao ??ciiai
aaiaco oa i?e ??cieo ooieoe?iiaeueieo noaiao, cie?aia a ia?auaiethaaieo
e?ioiaeanoi?aeieo e?i?yo ethaeeie, a ia?auaiethaaieo e?i?yo ieoa/i?
e?ioiie, a ia?aeiieo ee?oeiao ?aeo na/iaiai i?oo?a oa ?aeo ie?ee
ethaeeie, a iiiiioeeaa?ao ia?eoa??eii? e?ia? caei?iaeo aeiii??a oa
oai?eo ia a??oni? ?ioaeoe??, a i?e?iaeieo e?ea?ieo ee?oeiao caei?iaeo oa
oai?eo ethaeae oa a e?ioioeeoao, ye? ?io?eueo?othoue iooeeie;

— i?inoaaeeoe aca?iiae?th ?aoeii?ae?a c nenoaiith ?OI a ia?auaiethaaieo
e?i?yo ee?oei oa a ee?oeiao ?aeo na/iaiai i?oo?a, a oaeiae
i?iaiae?coaaoe iiaeeeaino? iiaeoeyoe?? aoaeo?a ?OI ?aoeii?aeaie ye a
iooeeiieo ee?oeiao, oae ? i?e o?ii?/ieo a??onieo ?ioaeoe?yo ethaeeie;

-i?iaiae?coaaoe ooieoe?iioaaiiy 2-5A neioaoace, ia iieaeoey?iiio ??ai?,
cie?aia i?iaiae?coaaoe oi?ie neioaciaaiiai i?iaeoeoo oa i?e?iaeo
aeoeaaoi??a oa?iaioo.

Iaoeiaa iiaecia iaea?aeaieo ?acoeueoao?a. Iaea?aeaii iia? aeai? uiaei
noaio nenoaie 2-5A a iooeeiieo ee?oeiao o oai?eo ia ?ae ie?ee oa ?ae
na/iaiai i?oo?a, a oaeiae a iiiiioeeaa?ao ia?eoa??eii? e?ia? caei?iaeo ?
oai?eo ethaeae a ni?anoaaeaii? c aiaeia?/ieie aeaieie aeey
ia?auaiethaaieo e?i?e iooeeiieo ee?oei. Aia?oa i?iaiae?ciaaii
ni?eeiyoeea?noue ee?oei ?aeo na/iaiai i?oo?a oa ?aeo ie?ee ethaeeie aei
??cieo oei?a ?aeiia?iaioieo ?OI ca aecia/aiiyi aeoeaiino? ?iaeoeiaaii?
2-5A neioaoace. ?acoeueoaoe ?iaioe na?ae/aoue i?i iiaeeeaino?
canoinoaaiiy iaoiaeo aecia/aiiy 2-5A neioaoace aeey iaea?aeaiiy
ia’?eoeaieo aeaieo uiaei ni?eeiyoeeaino? ye iooeeiieo ee?oei, oae ?
aoaeoi?ieo ee?oei ?ioiii? nenoaie aei ae?? ??cieo oei?a ?OI. I?iaaaeaii
ii??aiyeueia aea/aiiy ??ai?a aacaeueii? oa ?iaeoeiaaii? aeoeaiino?
oa?iaioo a ia?auaiethaaieo e?i?yo ee?oei ??ciiai aaiaco, a ia?aeiieo
ee?oeiao iooeei oa a aoaeoi?ieo ee?oeiao ?ioiii? nenoaie caei?iaeo
ethaeae, oai?eo ia iieio?ieia?/io iaoieia?th oa oai?eo ia a??oniee
aaiaoeo; i?iaiae?ciaai? ni?aa?aeiioaiiy i?ae aacaeueiith oa
?iaeoeiaaiith aeoeai?noth 2-5A neioaoace a ??cieo nenoaiao. Iieacaii, ui
ni?aa?aeiioaiiy i?ae aacaeueieie oa ?iaeoeiaaieie ??aiyie aeoeaiino?
2-5A neioaoace a iiiiioeeaa?ao ia?eoa??eii? e?ia? oa ia?aeiieo
eoeueoo?ao iooeeiieo ee?oei i?eioeeiiai a?ae??ciy?oueny a?ae oaeiai ae
ni?aa?aeiioaiiy a iecoe? ia?auaiethaaieo e?i?e iooeeiieo ee?oei ??ciiai
aaiaco. I?iaeaiiino?iaaii ei?aeyoe?? i?ae ooioe?iiaeueiith
ni?iiiaei?noth aoaeoi?ieo ee?oei ?ioiii? nenoaie, cie?aia i?e?iaeieo
e?ea??a oa e?ioioeeo?a, ye? ?io?eueo?othoue iooeeie, i?e ae?? ?OI, oa
?iaeoeoe??th a oeeo ee?oeiao 2-5A neioaoace. Iieacaii, ui ni?eueia ae?y
?aoeii?ae?a oa ?OI ye a eoeueoo?ao ia?auaiethaaieo e?i?e, oae ? a
ia?aeiieo eoeueoo?ao ?aeo na/iaiai i?oo?a iiaea i?ecaiaeeoe aei
neia?a?/ieo aoaeo?a uiaei c?inoaiiy ??ai?a ?iaeoeiaaii? aeoeaiino? 2-5A
neioaoace. Anoaiiaeaii, ui ?aoeii?aee iiaeooue ca iaaieo oiia neoaoaaoe
ca ?iaeoeoi?e ?OI ethaeeie, a oaeiae i?eai?/oaaoe ?ai?iaeoeoe?th ye
?ioaa?iaaieo aiaeiaaiieo ?ao?ia??on?a, oae ? a??ono ?ioiiaeao?oeeoo
ethaeeie.

I?e aea/aii? iieaeoey?ieo aniaeo?a ooieoe?iioaaiiy 2-5A neioaoace aia?oa
aoei iieacaii, ui i?aia?aoe o?IE iiaeooue aoaeoeaii i?aaeoe ca aeoeaaoi?
oeueiai oa?iaioo, ui aeicaiey? ia?aaeaa/eoe iiaeeeaino? oaeiai
ooieoe?iioaaiiy o?IE ? a i?e?iaeieo oiiaao. Iaea?aeai? aeai? iathoue
aaaeeeaa cia/aiiy aeey ?ice?eooy iaoai?ci?a ooieoe?iioaaiiy 2-5A
neioaoace a ee?oeiao a ii?i? oa i?e iaoieia?/ieo noaiao i?e a?aenooiino?
a??onii? ?ioaeoe??.

A i?ioean? aeeiiaiiy ?iaioe aia?oa aoei iaea?aeaii na??th
ia?auaiethaaieo e?i?e ieoa/eo ee?oei c o?ainieaioiaaieo e?ioii oa
ioa?aeoa?eciaaii ?ao?ia??one, ye? i?iaeoeothoueny oeeie ee?oeiaie.

I?aeoe/ia cia/aiiy iaea?aeaieo ?acoeueoao?a. Iaoiae aecia/aiiy
aeoeaiino? 2-5A neioaoace, iiaeeo?eiaaiee noiniaii ia?aeiieo eoeueoo?
iooeeiieo ee?oei oa iiiiioeeaa??a ia?eoa??eii? e?ia?, aoei ai?iaiaaii a
ee?ieoe? Oe?a?inueeiai IAe? o?ieia?? ? iao?ieia?? oa Ee?anuee?e
i?nuee?e iieieia?/i?e e?ea?i? aeey aiae?co ni?eeiyoeeaino? aei ?OI
iooeei oai?eo ia ?ae na/iaiai i?oo?a, ye? i?aeeyaaee eiia?iiaai?e
oa?ai?? ?c canoinoaaiiyi i?aia?aoo ?aeiia?iaioiiai ?OI aeueoa. Aeai?,
iaea?aeai? a i?ioean? aeeiiaiiy ?iaioe, aoee aeei?enoai? a iiaeaeueoeo
aeine?aeaeaiiyo, ye? i?iaiaeyoueny a IAe? o?ieia?? ? iao?ieia?? , c
iaoith canoinoaaiiy oeueiai ia?aiao?o aeey iii?oi?eiao
?ioa?oa?iiioa?ai??. Iaoiaeeea aecia/aiiy neioaoacii? aeoeaiino? oa
iaea?aeai? ?acoeueoaoe aoee ai?iaaaeaeai? a IAe? ai?aeai?ieia?? oa
?ioaeoe?eieo oai?ia aeey ne?ei?iao neioaoe/ieo oa i?e?iaeieo ?a/iaei ye
iiaeeeaeo ?iaeoeoi??a ?OI. ?acoeueoaoe uiaei aca?iiae?? ?aoeii?ae?a c
nenoaiith ?OI iiaeooue iaoe i?aeoe/ia cia/aiiy aeey ?ic?iaee iaoiae?a
eiia?iiaaii? oa?ai?? c aeei?enoaiiyi ?aoeii?ae?a oa ?OI. Iaea?aeai?
ia?auaiethaai? e?i?? ee?oei II, ye? iiaeooue neoaoaaoe ca iiaeaeue,
i?eaeaoio aeey iaeii/aniiai aea/aiiy aieeao ?OI oa iiaeoethth/eo
oaeoi??a ia i?ie?oa?aoe?th ee?oei ? ia ?ai?iaeoeoe?th ?ioaa?iaaieo
a??on?a, ai?iaaaeaeai? a eaai?aoi??yo ?inoeoooo aenia?eiaioaeueii?
iaoieia??, iieieia?? ? ?aae?ia?ieia??, ?inoeoooo iieaeoey?ii? a?ieia?? ?
aaiaoeee oa IAe? ai?aeai?ieia?? oa ?ioaeoe?eieo oai?ia.

Ai?iaaoe?y ?acoeueoao?a aeine?aeaeaiiy. Iaea?aeai? ?acoeueoaoe aoee
i?aaenoaaeai? ia oaeeo iaoe?iiaeueieo oa i?aeia?iaeieo eiioa?aioe?yo oa
neiiiceoiao:

??? Ananithcia eiioa?aioe?y «No/ani? iaoiaee ii?oieia?/iiai
aeine?aeaeaiiy a oai?aoe/i?e oa i?aeoe/i?e iieieia??» (Oa?e?n? 1983);
neiiiceoi c i?io?eaeoeee oa e?eoaaiiy a??onieo ?ioaeoe?e (Ethae?oea,
*aoineiaa//eia 1985); ui??/i? cai?e I?aeia?iaeiiai oiaa?enoaa c
aeine?aeaeaiue ii ?ioa?oa?iio (ISIR) (I?oeoea, O?aioe?y 1991 oa Oi?iioi,
Eaiaaea 1992); I?aeia?iaeiee neiiic?oi c aea?aieia?? oa ee?i?/ii?
?ioiieia?? (Aeia-Aoa, Eacaonoai 1992); 8-e I?aeia?iaeiee eiia?an c
?ioiieia?? (Aoaeaiaoo, Oai?ueia 1992); 4-a I?aeia?iaeia eiioa?aioe?y c
i?ioe?aeiaeo aeine?aeaeaiue (?aoeiiii, A?aoe?y 1992); 1-e c’?cae
?ioiieia?a ?in?? (Iiainea??nuee, ?in?y 1992); 9-a I?aeia?iaeia
eiioa?aioe?y c NI?Aeo (Aa?e?i, I?ia//eia 1993); iaoeiai-i?aeoe/ia
eiioa?aioe?y iieieia?a Oe?a?ie (Aeiiaoeuee 1993); 7-e Ieaioi iaoeiaiai
oiaa?enoaa o?ieia?a Oe?a?ie (Ee?a 1993); 18-e I?aeia?iaeiee eiia?an c
o?i?ioa?ai?? (Noieaieuei, Oaaoe?y 1993); 19-e I?aeia?iaeiee eiia?an c
o?i?ioa?ai?? (Iii?aaeue, Eaiaaea 1995); 1-a iaoeiai-i?aeoe/ia
eiioa?aioe?y c i?iaeai A?E/NI?Ae c i?aeia?iaeiith o/anoth (Ee?a, Oe?a?ia
1995); 9-e I?aeia?iaeiee eiia?an c e?eoaaiiy ?aeo (Ia?eae, O?aioe?y
1999).

Ioae?eaoe?? ?acoeueoao?a aeine?aeaeaiue. Ca ?acoeueoaoaie i?iaaaeaieo
aeine?aeaeaiue iioae?eiaaii 4 aeo?iaeueieo noaoo? a i?ia?aeieo oaoiaeo
aeaeaiiyo (iaeia c ieo — a caei?aeiiiiio aeaeaii?), 4 noaoo? a ca??ieeao
i?aoeue (iaeia c ieo — a caei?aeiiiiio aeaeaii?) oa 13 oac aeiiia?aeae a
a?o/eciyieo oa i?aeia?iaeieo ca??ieeao iaoa??ae?a eiioa?aioe?e oa
neiiic?oi?a.

Ca’ycie ?iaioe c iaoeiaeie i?ia?aiaie, ieaiaie, oaiaie. Aeine?aeaeaiiy
i?iaiaeeeenue ia aac? ?inoeoooo aenia?eiaioaeueii? iaoieia??, iieieia??
? ?aae?ia?ieia?? ?i.?.?.Eaaaoeueeiai IAI Oe?a?ie o a?aeiia?aeiino? c
oaiaoeeith iaoeiaeo aeine?aeaeaiue ?inoeoooo, i?ia?aiith AeEIO Oe?a?ie,
a oaeiae Aea?aeaaiith i?ia?aiith aeine?aeaeaiue c NI?Aeo.
Aeine?aeaeaiiy aoee oaeiae ocaiaeaeaii? c oaiaoeeaie IAe? ai?aeai?ieia??
oa ?ioaeoe?eieo oai?ia ?i. E.A?iiaoaanueeiai IIC Oe?a?ie oa ?inoeoooo
o?ieia?? oa iao?ieia?? AII Oe?a?ie, ia aac? yeeo aoei aeeiiaii /anoeio
aeine?aeaeaiue. Ia?auaiethaai? e?i?? ee?oei ieoa/i? e?ioiie, ye?
i?iaeoeothoue aiaeiaaii? ?ao?ia??one, aoee iaea?aeai? ia iniia? ooai?a
e?ioii, ui aoee ?iaeoeiaai? Aan.megaterium H. a ?aieao aeine?aeaeaiue,
caii/aoeiaaieo /e.-ei?. IAI Oe?a?ie Ae.A.Caooeith.

Iniaenoee aianie caeiaoaa/a. Caeiaoaa/ai iniaenoi aoei aecia/aii ieai
aeine?aeaeaiue oa aeeiiaii a?eueoo /anoeio aenia?eiaioaeueii? ?iaioe,
cie?aia eiiieaen a??onieia?/ieo aeine?aeaeaiue oa aenia?eiaioe c
aecia/aiiy aeoeaiino? 2-5A neioaoace a ia?aeiieo iooeeiieo ee?oeiao,
iiiiioeeaa?ao ia?eoa??eii? e?ia? caei?iaeo aeiii??a oa oai?eo, a oaeiae
a ia?auaiethaaieo e?i?yo iooeeiieo ee?oei ??ciiai aaiaco, aeeth/ath/e ?
e?i?? ieoa/eo e?ioii, aia?oa iaea?aeaieo aaoi?ii c iooeei, ?iaeoeiaaieo
aaeoa??yie. Caeiaoaa/ oaeiae iniaenoi aeeiiaa aenia?eiaioe ii
aecia/aiith aeoeaiino? ?OI a eoeueoo?aeuei?e ??aeei? ia?aeiieo oa
ia?auaiethaaieo e?i?e ee?oei oa a ne?iaaooe? caei?iaeo aeiii??a ?
oai?eo, a oaeiae aenia?eiaioe c aecia/aiiy ooieoe?iiaeueii? aeoeaiino?
aoaeoi?ieo ee?oei ?ioiii? nenoaie. Caeiaoaa/ aeeiiaa noaoenoe/io ia?iaeo
iaea?aeaieo aeaieo oa i?eeiaa aaciina?aaeith o/anoue a ioi?ieaii?
iaoa??ae?a oa i?aeaioiaoe? ?o aei ioae?eaoe??.

Ia ie?aieo aoaiao ?iaioe aeine?aeaeaiiy i?iaiaeeeenue ni?eueii c ?ioeie
ni?a?ia?oieeaie. Aeine?aeaeaiiy c ee?oeiaie, ui i?iaeoeothoue A?E,
i?iaiaeeee ia aac? eaai?aoi??? caaaeueii? a??onieia?? IAe?
ai?aeai?ieia?? oa ?ioaeoe?eieo oai?ia ?i. E.A?iiaoaanueeiai IIC Oe?a?ie
ca o/anoth ae.i.i. N.?eaaeei. Aeine?aeaeaiiy aeanoeainoae aiaeiaaiieo
?ao?ia??on?a ieoae i?iaiaeeeenue ?acii c e.i.i. I.Aa?oaoeueeei (?AII?).
I?e i?iaaaeaii? aeine?aeaeaiue aoee aeei?enoai? i?ea?iaeuei?
e?i?aeii-a?oai?ii? eiiiiceoe??, ?ic?iaeai? e.i.i. ?.Oa?oeueeei (?AII?).
Aeaeo?ioi?aoe/iee aiae?c neioaciaaieo ie?aiaaeai?eao?a aoei i?iaaaeaii
ca aeiiiiiaith e.a.i. C.Iao?ooaiei (?inoeooo iieaeoey?ii? a?ieia?? ?
aaiaoeee IAIO). I?aia?aoe o?IE, ye? aoee iiia?aaeiuei aeae?eai? oa
ioa?aeoa?eciaai?, aoee etha’ycii iaaeai? e.i.i. A.Aa?oaoeueeith,
aeine?aeaeaiiy ?ie? i?e?iaeieo aeoeaaoi??a oa?iaio?a nenoaie ?OI aoee
i?iaaaeai? ca ?? etha’yciiai ni?eyiiy. Ee?i?/iee oa a?io?i?/iee aiae?c o
oai?eo ia a??oniee aaiaoeo aoei i?iaaaeaii ae.i.i. N.Oaaei?/aiei
(ee?i?ea IAe? ai?aeai?ieia?? oa ?ioaeoe?eieo oai?ia). Ii?oieia?/iee
aiae?c i?aia?ao?a ?aeo na/iaiai i?oo?a oa ?aeo ie?ee oai?eo, ye?
ia?aaoaaee ia e?eoaaii? a Oe?a?inueeiio IAe? o?ieia?? ? iao?ieia??, aoei
aeeiiaii ia aac? iieio?ieia?/iiai a?aeae?eaiiy Ee?anueei? i?nueei?
iieieia?/ii? e?ea?i? (ea??aiee ae.i.i. A.Ee?iaiei). A?aea?? oai?eo oa
iaea?aeaiiy iia?aoe?eiiai iaoa??aeo i?iaiaeeee ca ni?eyiiy
e.i.i. A.A?eai?aiea.

No?oeoo?a oa ianya aeena?oaoe??. Aeena?oaoe?th aeeeaaeaii ia 188 noi?.
iaoeiiieniiai oaenoo. Aiia neeaaea?oueny c anooio, iaeyaeo e?oa?aoo?e (2
?icae?ee), /ioe?ueio ?icae?e?a aeanieo aeine?aeaeaiue, iaaiai?aiiy
?acoeueoao?a, aeniiae?a oa nieneo aeei?enoaieo aeaea?ae, yeee caeia? 30
noi?. ? i?noeoue 298 aeaea?ae. Aeena?oaoe?y i?noeoue 18 oaaeeoeue oa 20
?ethno?aoe?e.

CI?NO ?IAIOE

Iaoa??aee ? iaoiaee. Aeine?aeaeaiiy i?iaiaeeee ia ia?aeiieo eoeueoo?ao
iiiiioeeaa??a ia?eoa??eii? e?ia?, ia?aeiieo eoeueoo?ao ee?oei ?aeo
na/iaiai i?oo?a oa ie?ee oa ia?auaiethaaieo e?i?yo iooeeiieo ee?oei
??ciiai aaiaco. Anueiai aoei i?iaiae?ciaaii 12 ia?aeiieo eoeueoo?
iiiiioeeaa??a ia?eoa??eii? e?ia? caei?iaeo aeiii??a, 20 ia?aeiieo
eoeueoo? iiiiioeeaa??a ia?eoa??eii? e?ia? oai?eo ia a??oniee aaiaoeo A,
7 ia?aeiieo eoeueoo? ee?oei ?aeo ie?ee, 29 ia?aeiieo eoeueoo? ?aeo
na/iaiai i?oo?a, 18 ia?aeiieo eoeueoo?ao iiiiioeeaa??a ia?eoa??eii?
e?ia? oai?eo ia ?ae na/iaiai i?oo?a, 5 eoeueoo? e?ioioeeo?a, ye?
?io?eueo?othoue iooeeie (?ae ie?ee). Iieacieee ?ioa?oa?iiiaiai noaoono
(??ai? ?OI a ne?iaaooe? oa ?iaeoeoe?th ?OI a iiiiioeeaa?ao ia?eoa??eii?
e?ia?) aiae?coaaee o 34 caei?iaeo aeiii??a oa 34 oai?eo ia ?ae na/iaiai
i?oo?a. A i?ioean? aeeiiaiiy aeine?aeaeaiue aaoi?ii aoei iaea?aeaii 4
noaa?eueieo ia?auaiethaaieo e?i?? ee?oei ieoa/eo e?ioii.

A??onieia?/i? aeine?aeaeaiiy i?iaaaeaii ye c aiaeiaaiieie ?ao?ia??onaie,
anioe?eiaaieie c ee?oeiaie ieoa/eo e?ioii, oae ? c A?E a oiiaao aino?i?
oa o?ii?/ii? ?ioaeoe?? eoeueoo? e?ioiaeanoi?aeieo e?i?e ethaeeie.

A ?iaio? aeei?enoaii ?aeiia?iaioi? ?OI ethaeeie (aeueoa, aaoa oa aaiia),
?aeiia?iaioiee ?ioa?eaee?i-2 oa i?e?iaei? i?aia?aoe ieoa/iai ?OI,
?iaeoeiaaiiai in vitro ? in vivo.

A aeine?aeaeoaaieo eoeueoo?ao aoei i?iaiae?ciaaii ye aacaeueio
aeoeai?noue 2-5A neioaoace, oae ? ??ai? ?? ?iaeoeoe?? i?e ae?? ?OI.
Aeoeai?noue oa?iaioo aecia/aee ca ??aiai eiiaa?n?? 3I-AOO aei 2-5A. Aeey
o?aeoe?iioaaiiy neioaciaaiiai 2-5A a?ae iaaeeth/aiiai iiia?aaeieea
aeei?enoiaoaaee o?iiaoia?ao?th ia i?i?eieiieao AeAAA-oeaetheice ?c
nooi?i/aoith aethoe??th oa o?iiaoia?ao?th ia AeAAA-oeaetheic? a
noniaic?? a noaoe/iiio aa??aio?. Ie??i aecia/aiiy noia?ii? aeoeaiino?
2-5A neioaoace ca ?ioaa?aeueiei iieacieeii, i?iaiaeeee oaeiae aiae?c
i?iaeoeo?a neioaoacii? ?aaeoe?? ca aeiiiiiaith oiieioa?iai?
o?iiaoia?ao?? oa aeaeo?ioi?aco a iie?ae?eeai?aeiiio aae? c na/iaeiith (c
aeei?enoaiiyi aeueoa-32?-AOO ye i?/aiiai iiia?aaeieea).

?OI oeo?oaaee i?ioe 100 OOeIAe50 a??ono aaceeoey?iiai noiiaoeoo (AAN) ia
ee?oeiao L41 (?OI ethaeeie) oa L929 (?OI ieoae). Oeioaaiiy ?OI
i?iaiaeeee ye ca e?eoa???i eeneioieaa?eueiino?, oae ? c aeei?enoaiiyi
iiiieeiiaeueieo aioeo?e i?ioe ethaenueeiai ?OI aeueoa.

Aecia/aiiy aeoeaiino? i?e?iaeieo e?ea??a i?iaiaeeee a oano? c
3I-o?eaeeiii c aeei?enoaiiyi ee?oei E562 ye i?oaiae. Aecia/aiiy
oeeoie?oe/ii? aeoeaiino? e?ioioeeo?a, ye? ?io?eueo?othoue iooeeie,
i?iaiaeeee a oano? c 3I-o?eaeeiii i?ioe ee?oei Raji.

?acoeueoaoe oa ?o iaaiai?aiiy. Aeey aecia/aiiy ni?eeiyoeeaino? ee?oei
aei aeciaaiiiai ?OI aoei i?iaaaeaii ii??aiyeueiee aiae?c aaee/ei
aacaeueii? aeoeaiino? 2-5A neioaoace oa ni?aa?aeiioaiiy i?ae ??aiyie
aacaeueii? oa ?iaeoeiaaii? ?OI aeoeaiino?. Caaaeai? aeai? ii aecia/aiith
aacaeueii? oa ?iaeoeiaaii? aeoeaiino? 2-5A neioaoace a ia?aeiieo
eoeueoo?ao iiiiioeeaa??a ia?eoa??eii? e?ia? oa a aeayeeo c
aeine?aeaeoaaieo ia?auaiethaaieo e?i?e e?ioiaeanoi?aeieo ee?oei
iaaaaeai? a oaaeeoe? 1.

A ia?aeiieo eoeueoo?ao iiiiioeeaa??a ia?eoa??eii? e?ia? caei?iaeo
aeiii??a aaee/eia aacaeueii? aeoeaiino? 2-5A neioaoace aoea a?aeiinii
iecueeith. Ia?iaea ee?oei ?OI a on?o aeiaaeeao i?ecaiaeeea aei
i?aeaeuaiiy oeueiai ??aiy, i?e/iio iaea?eueo? cia/aiiy ?iaeoeiaaii?
aeoeaiino? niinoa??aaee i?e canoinoaaii? ?OI aeueoa. Ia aoei aeiaeiiai
aeiaaeeo, eiee a ee?oeie aeiii??a ia a?ae?aaaoaaee a ia oie /e ?ioee
?OI, oi/a iaaii? ei?aeyoe?? i?ae aeo?aeiei ??aiai aeoeaiino? oa?iaioo oa
e?aoi?noth eiai i?aeaeuaiiy i?e ae?? ?OI ia ?nioaaei.

I?e aea/aii? oeo aea iieaciee?a a iiiiioeeaa?ao ia?eoa??eii? e?ia?
oai?eo ia a??oniee aaiaoeo A, aoei anoaiiaeaii, ui o aeayeeo oai?eo
aacaeueiee ??aaiue ia a?ae??ciy?oueny nooo?ai a?ae oaeiai o caei?iaeo
aeiii??a, a oie /an ye a ?ioeo aeiaaeeao niinoa??aa?oueny i?aeaeuaiiy
aacaeueieo ??ai?a iaeaea ia ii?yaeie. Oa?aeoa? ?iaeoeoe?? oa?iaioo i?ney
?ieoaaoe?? ee?oei c ?OI ?ic??ciyany a caeaaeiino? a?ae aeo?aeieo ??ai?a
aeoeaiino? oa?iaioo, a naia, a i?aea?oi? c aenieeie cia/aiiyie
aacaeueieo ??ai?a aeoeaiino? aeey aeiaeiiai c ?OI ia aoei a?aecia/aii
iiaeaeueoiai nooo?aiai i?aeaeuaiiy aeoeaiino? 2-5A neioaoace.

Cia/aiiy ?ioaa?aeueii? aacaeueii? aeoeaiino? 2-5A neioaoace a
iiiiioeeaa?ao ia?eoa??eii? e?ia? oai?eo ia ?ae na/iaiai i?oo?a aoee ia
iaaaaaoi aeueie ca oae? a iiiiioeeaa?ao ia?eoa??eii? e?ia? caei?iaeo
aeiii??a. I?aeaeuaiiy ??ai?a aeoeaiino? oa?iaioo i?ney ?ieoaaoe??
iiiiioeeaa??a ia?eoa??eii? e?ia? oaeeo oai?eo c aoaeue-yeei c
?aeiia?iaioieo ?OI ae?aaeaia a iaio?e i??? a ii??aiyii? c a?aeiia?aeieie
iieacieeaie aeey caei?iaeo aeiii??a.

Aiae?c iieaciee?a aeoeaiino? 2-5A neioaoace a ia?auaiethaaieo e?i?yo
o?ainoi?iiaaieo ee?oei iieacaa, ui a aaaaoueio c ieo ??ai? aacaeueii?
aeoeaiino? nooo?ai ca?eueoai?, ?acii c oei iiaeaeueoa c?inoaiiy
aeoeaiino? i?e ?iaeoeoe?? ?OI nyaa? a ?yae? aeiaaee?a aeineoue cia/ieo
??ai?a. Oae, cie?aia, a ee?oeiao Raji aeoeai?noue 2-5A neioaoace i?ney
?ieoaaoe?? ee?oei c ?OI aeueoa ca?eueooaaeanue i?eaeecii a 90 ?ac?a.

Na?aaei?e iieaciee aacaeueii? aeoeaiino? 2-5A neioaoace a ee?oeiao ?aeo
ie?ee aoa aeaui aeuei, i?ae a iiiiioeeaa?ao ia?eoa??eii? e?ia? caei?iaeo
aeiii??a, aea cia/ii ieae/ei a?ae aacaeueieo cia/aiue a ia?auaiethaaieo
e?i?yo ee?oei ??ciiai aaiaco. I?aeoe/ii oae? ae aeai? aoee iaea?aeai? ?
i?e aecia/aii? aacaeueii? aeoeaiino? oa?iaioo a ee?oeiao ?aeo na/iaiai
i?oo?a (oaaeeoey 2). ??ai? ?iaeoeiaaii? aeoeaiino? oa?iaioo na?ae/aoue
i?i oa, ui a aaaaoueio aeiaaeeao ee?oeie ?aeo ie?ee oa ?aeo na/iaiai
i?oo?a ? ni?eeiyoeeaeie aei ae?? ?OI, oi/a a?aeiiniee ??aaiue c?inoaiiy
aoa ii??aiyii iaaaeeeei. I?e aiae?c? ?iaeea?aeoaeueieo aeaieo a
ia?aeiieo eoeueoo?ao ?aeo ie?ee iiaeia aoei i?inoaaeeoe cai?ioio
caeaaei?noue e?aoiino? c?inoaiiy aeoeaiino? oa?iaioo i?e ae?? ?OI aeueoa
/e aaoa a?ae aeo?aeiiai ??aiy aeoeaiino?. O aeiaaeeo ?aeo na/iaiai
i?oo?a na?aaeiy e?aoi?noue ca?eueoaiiy ??ai?a aeoeaiino? i?ae aieeaii
?OI ??cieo oei?a aoea aeuith a ii??aiyii? c ee?oeiaie ?aeo ie?ee.
E?aoi?noue ca?eueoaiiy aeoeaiino? neioaoace aoea a?eueo cia/iith i?e
canoinoaaii? ?OI aaoa, i?e/iio iaea?eueo ae?aaeaiei aoaeo aoa a a?oiao
/ieia?e?a noa?oeo ca 50 ?ie?a.

Oaaeeoey 1

Aeo?aei? oa ?iaeoeiaai? ??ai? aeoeaiino? 2-5A neioaoace a iiiiioeeaa?ao
ia?eoa??eii? e?ia? caei?iaeo aeiii??a, oai?eo ia a??oniee aaiaoeo A,
oai?eo ia ?ae na/iaiai i?oo?a oa a e?ioiaeanoi?aeieo ee?oeiao
ia?auaiethaaieo e?i?e

Aeaea?aei ee?oei Aeo?aeiee ??aaiue aeoeaiino?* ??aaiue aeoeaiino? i?ney
ia?iaee ?OI*

?OI aeueoa ?OI aaoa ?OI aaiia

Caei?ia? aeiii?e 12,2(8,7 80,0(57,9 41,0(30,5 39,2(19,7

Oai?? ia a??oniee aaiaoeo A 1-a i?aea?oia 104,7( 25,5 147,6(31,1**
117,0(18,8** 135,8(23,2**

2-a i?aea?oia 13,5(3,6*** 78,0(33.1 39,3(13,4 44,2(6,9

Oai?? ia ?ae na/iaiai i?oo?a 19,2(6,8*** 42,1(15,3 31,5(12,6**
37,5(12,7**

Ia?auaiethaai? e?i?? e?ioiaeanoi?aeieo ee?oei

Raji 36±4 3250±1525 _ 85±32

NAI 75±12 1870±943 _ 168±54

*- aeoeai?noue 2-5A neioaoace ae?aaeaee a iiieue 3I-AOO, eiiaa?oiaaiiai
aei 2-5A ca 1 aiaeeio ia 105 ee?oei

**-??cieoey a ii??aiyii? c aeo?aeiei ??aiai iaaeinoia??ia (?>0,05)

***-??cieoey a ii??aiyii? c iieacieeaie o caei?iaeo aeiii??a
iaaeinoia??ia (?>0,05)

Aoei i?iaiae?ciaaii oaeiae ni?aa?aeiioaiiy i?ae ??aiyie aacaeueii? oa
?iaeoeiaaii? aeoeaiino? 2-5A neioaoace oa ??aiyie aiaeiaaiiiai ?OI, a
oaeiae aeayeeie iieacieeaie, ui oa?aeoa?ecothoue ooieoe?iiaeueio
ni?iiiaei?noue aoaeoi?ieo ee?oei ?ioiii? nenoaie. A ia?auaiethaaieo
e?i?yo ye a??oni?iaeoeoth/eo, oae ? a??oniai?iaeoeoth/eo iooeeiieo
ee?oei, iacaaaeath/e ia i?aeaeuai? ??ai? aacaeueii? aeoeaiino? oa?iaioo,
oeo?e aiaeiaaiiiai ?OI a eoeueoo?aeueiiio na?aaeiaeu? aoee ia iaae?
/ooeeaino? aecia/aiiy.

O oai?eo ia ?ae na/iaiai i?oo?a a?aeiinia ciaioaiiy ni?eeiyoeeaino?
iiiiioeeaa??a ia?eoa??eii? e?ia? aei ?OI ca e?eoa??yie ?iaeoeoe?? a ieo
2-5A neioaoace noi?iaiaeaeo?oueny ca?eueoaiiyi ??ai?a ?OI aaiia a
ne?iaaooe? e?ia? oa ciaioaiiyi ooieoe?iiaeueii? ni?iiiaeiino? i?e?iaeieo
e?ea?ieo ee?oei, yea /anoeiai a?aeiiaeth?oueny i?e ?o ?ieoaaoe?? c ?OI
aeueoa (?en. 1).

Oaaeeoey 2

Aeo?aei? oa ?iaeoeiaai? ??ai? aeoeaiino? 2-5A neioaoace a ia?aeiieo
eoeueoo?ao ?aeo ie?ee oa ?aeo na/iaiai i?oo?a*

A?oia oai?eo Aeo?aeiee ??aaiue aeoeaiino? ??aaiue aeoeaiino? i?ney
ia?iaee ?OI

?OI aeueoa ?OI aaoa ?OI aaiia

?ae ie?ee

An? oai?? 30(16 106(60 94(48 73(39

?ae na/iaiai i?oo?a

*ieia?ee iieiaeo? 50 ?ie?a 15(6 73(38 92(33 63(23

AE?iee iieiaeo? 50 ?ie?a 27(10 102(24 136(77 79(15

*ieia?ee noa?o? ca 50 ?ie?a 23(17 151(35 238(43 95(20

AE?iee noa?o? ca 50 ?ie?a 17(10 85( 21 185(7 85(15

Oai??, yeei i?iaiaeeee ia?aaeiia?aoe?ei? ?inoeeyoe?? ?OI aeueoa 25(8
128(23 173(33 102(15

*- aeoeai?noue 2-5A neioaoace ae?aaeaee a iiieue 3I-AOO, eiiaa?oiaaiiai
aei 2-5A ca 1 aiaeeio ia 105 ee?oei

?ieoaaoe?y c ?OI aeueoa eoeueoo?, iaea?aeaieo i?e eoeueoeaoaaii? in
vitro a i?enooiino? ?E-2 e?ioioeeo?a, ye? ?io?eueo?othoue ?aeia? iooeeie
ie?ee, i?ecaiaeeoue aei ca?eueoaiiy iieaciee?a ?o oeeoie?oe/ii?
aeoeaiino?, ui noi?iaiaeaeo?oueny ca?eueoaiiyi ??ai?a aeoeaiino?
?iaeoeiaaii? 2-5A neioaoace.

Ca aeiiiiiaith aeaeo?ioi?aco a iie?ae?eeai?aeiiio aae? aoei
i?iaiae?ciaaii i?io?e? ie?aiaaeai?eao?a, neioaciaaieo a aacee?oeiieo
nenoaiao. A oiiaao noaiaea?oii? neioaoacii? ?aaeoe?? c e?caoaie ee?oei,
i?i?ieoaiaaieo c ?OI, aeyaeythoueny oeiia? oinoi?eeueiaai? oa
iaoinoi?eeueiaai? oi?ie ie?aiaaeai?eao?a, i?e/iio a aaaaoueio aeiaaeeao
ia?aaaaeathoue oinoi?eeueiaai? oi?ie. Aeeo/aiiy aeaieaioethaiai? ?IE c
?ieoaaoe?eii? noi?o? i?ecaiaeeoue aei iiaii? ao?aoe iaoinoi?eeueiaaieo
oi?i ie?aiaaeai?eaoo. Naia aeei?enoaiiy oeueiai iaoiaeo aiae?co
i?iaeoeo?a 2-5A neioaoacii? ?aaeoe?? aeicaieeei i?iaeaiiino?oaaoe
ca?eueoaiiy aeoeaiino? oa?iaioo a e?caoao, iaea?aeaieo c eoeueoo?
e?ioioeeo?a, ye? ?io?eueo?othoue iooeeie, ui i?iyaeyeinue ye a
ca?eueoaii? ?ioaineaiino? ?nioth/eo nioa 2-5A, oae ? a iiya?
aeiaeaoeiaeo nioa.

Aiae?c i?iaeoeo?a neioaoacii? ?aaeoe?? ca aeiiiiiaith oiieioa?iai?
o?iiaoia?ao?? oa aeaeo?ioi?aco aeicaieea i?iaeaiiino?oaaoe, ui i/euai?
i?aia?aoe o?IE iiaeooue i?aaeoe ca aeoeaaoi?e 2-5A neioaoace, oi/a aeey
aoaeoeaiiai neioaco iaiao?aeii aeei?enoiaoaaoe o?IE a e?eueeinoyo, ui
i?aeoe/ii ia ii?yaeie ia?aaeuothoue oae? aeey iie??-iie?Oe. Oi?ie
ie?aiaaeai?eao?a, ui neioacothoueny a i?enooiino? o?IE, iaei
a?ae??ciythoueny a?ae oeo, ui neioacothoueny a i?enooiino? iie??-iie?Oe.

?en. 1. Aieea ?OI ia aeoeai?noue i?e?iaeieo e?ea?ieo ee?oei oai?eo ia
?ae na/iaiai i?oo?a:1 — o caei?iaeo aeiii??a; 2-5 — o oai?eo ia ?ae
na/iaiai i?oo?a:2-aac ia?iaee ?OI; 3-ia?iaea ?OI aeueoa; 4-ia?iaea ?OI
aaoa; 5-ia?iaea ?OI aaiia. Oeeoioiene/i?noue — a e?oe/ieo iaeeieoeyo ia
107 ee?oei

Aca?iiae?th ?aoeii?ae?a c nenoaiith ?OI oa aaciina?aaei? aoaeoe
?aoeii?ae?a ia i?ie?oa?aoe?th ee?oei oa ?ai?iaeoeoe?th a??on?a aea/aee a
ia?aoaiethaaieo e?i?yo iooeeiieo ee?oei (a oiio /ene? ? a nenoaiao
?ioaa?iaaii? ?ao?ia??onii? ?ioaeoe??), a oaeiae a ia?aeiieo eoeueoo?ao
ee?oei ?aeo na/iaiai i?oo?a. ?aoeii?aee ni?aaeythoue iii?oiee
aaeuei?aiee aoaeo ia i?ie?oa?aoe?th ee?oei ieoa/i? e?ioiie (?en. 2). I?e
oeueiio a o?e aea nenoai? aaeueioaaiiy i?iaeoeoe?? aiaeiaaiieo
?ao?ia??on?a aoei aeyaeaii eeoa ca oiiae iino?eiiai i?aeo?eiaiiy
eoeueoo?e a aeniiiaioe?ei?e oac? ?inoo, i?e aeinyaiaii? eoeueoo?ith
noaoe?iia?ii? oace aoei aeyaeaii iaa?oue aeayea i?aeneeaiiy
?ai?iaeoeoe?? a??on?a.

Eoeueoeaoaaiiy A?E-?io?eiaaieo ee?oei a i?enooiino? ?aoeii?ae?a a
nenoaiao ye aino?i?, oae ? o?ii?/ii? ?ioaeoe?? ia noi?iaiaeaeo?oueny
iii?oieie ci?iaie aeni?an?? a??ono, aea i?e oeueiio a?aeaoaa?oueny
nooo?aa i?eai?/aiiy eiai ?ioaeoe?eiino? (oaae. 3).

Iiia?aaeiy ?ieoaaoe?y ee?oei Ia?-2 a i?enooiino? ?aoeii?ai? eeneioe
ni?e/eith? iioaioe?thaaiiy uiaei ianooiii? ?iaeoeoe?? neioaoace i?ae
aieeaii aeciaaiiiai ?OI aeueoa. Ca?eueoaiiy ??ai?a ?iaeoeiaaii?
aeoeaiino? neioaoace ? aeineoue nooo?aei ? iineoue aeicicaeaaeiee
oa?aeoa? (?en. 3).

Aiaeia?/iee aoaeo i?aeneeaiiy ?iaeoeoe?? neioaoace i?e ?ieoaoaaii? c
?aoeii?aith eeneioith oa ?OI aeueoa aoei aeyaeaii ? a ia?aeiieo
eoeueoo?ao iooeeiieo ee?oei aeayeeo oai?eo ia ?ae na/iaiai i?oo?a Oaeei
/eiii, aoaeoe iiaeoethaaiiy ae?? ?OI ?aoeii?aeaie a ia?aeiieo oa
ia?auaiethaaieo eoeueoo?ao iooeeiieo ee?oei iiaeooue /anoeiai
iiina?aaeeiaoaaoenue /a?ac nenoaio 2-5A.

Oaaeeoey 3.

Aieea ?OI oa ?aoeii?ae?a ia ?ai?iaeoeoe?th oa ?ioaeoe?ei?noue A?E a
o?ii?/ii ?io?eiaaieo ee?oeiao IO4/A???

I?aia?ao Aeni?an?y A?E ca oeo?ii ?24* ?ioaeoe?eiee oeo? ia ee?oeiao
IO4** Aeoeai?noue cai?ioii? o?aine?eioace***

( 1:102400 10-8 13,0

?OI aeueoa 1:51200 10-4 10,6

?aoeiieaoeaoao 1:25600 10-6 7,3

*- Oeo? ?24 aecia/aee iaoiaeii ?ioiioa?iaioiiai aiae?co

**-?ioaeoe?eiee oeo? A?E aecia/aee ye oaea e?aei? ?icaaaeaiiy
eoeueoo?aeueii? ??aeeie, i?e ?io?eoaaii? a yeiio eoeueoo? IO4 /a?ac 5
ae?a a eoeueoo?aeuei?e ??aeei? inoaii?o ua iiaeia aoei aeinoia??ii
aecia/eoe oeo? ?24

***- ?acoeueoaoe aecia/aiiy iaaaaeai? a oen.?ii./oa. aeeth/aiiy 3I-OOO
aei OOI-ia?ic/eiii? o?aeoe?? ia aeciaaii?e iao?eoe? iie? ?A -ie?ai aeO

?en.2. Aieea ?aoeii?ai? eeneioe ia i?ie?oa?aoe?th ee?oei e?ioiie II-1.

?en. 3. Aieea ?aoeii?ai? eeneioe (?E) ia ?iaeoeoe?th 2-5A neioaoace ?OI
aeueoa a ee?oeiao Ia?-2:1 — ee?oeie i?ieoeueoeaiaai? aac ?E oa aac ?OI;
2 — ee?oeie i?ieoeueoeaiaai? a i?enooiino? 10 ieiieue/e ?E aac ianooiii?
ia?iaee ?OI; 3 — ee?oeie i?ieoeueoeaiaai? a i?enooiino? 100 II/ie ?OI
aeueoa aac iiia?aaeiuei? ?ieoaaoe?? a i?enooiino? ?E; 4 — ee?oeie aoee
iiia?aaeiuei i?ieoeueoeaiaai? a i?enooiino? 1 ieiieue/ie ?E, a iio?i
ia?iaeai? 100 II/ie ?OI aeueoa; 5 — ee?oeie aoee iiia?aaeiuei
i?ieoeueoeaiaai? a i?enooiino? 10 ieiieue/ie ?E, a iio?i ia?iaeai? 100
II/ie ?OI aeueoa

AENIIAEE

1.I?iaaaeaii ii??aiyeueiee aiae?c caeaaeiino? i?ae aeo?aeieie oa
?iaeoeiaaieie ?OI ??aiyie 2-5A neioaoace a ia?auaiethaaieo e?i?yo oa
ia?aeiieo eoeueoo?ao iooeeiieo ee?oei ethaeeie, a iiiiioeeaa?ao
ia?eoa??eii? e?ia? caei?iaeo aeiii??a, iieio?ieia?/ieo oai?eo oa oai?eo
ia a??oniee aaiaoeo A. Iieacaii, ui ia?aeii? eoeueoo?e ee?oei ?aeo
na/iaiai i?oo?a oa ?aeo ie?ee a a?eueoino? aeiaaee?a ni?eeiyoeea? aei
ae?? ?OI. ??aaiue ?iaeoeoe?? 2-5A neioaoace a iiiiioeeaa?ao ia?eoa??eii?
e?ia? iieieia?/ieo oai?eo ieae/?e ca oaeee o caei?iaeo ethaeae, a
iiiiioeeaa?e ia?eoa??eii? e?ia? cia/ii? /anoeie oai?eo ia a??oniee
aaiaoeo A c i?aeaeuaieie aeo?aeieie ??aiyie aeoeaiino? oa?iaioo aoee
?ao?aeoa?ieie aei ae?? ?OI ca oeei iieacieeii.

2.Anoaiiaeaii, ui ciaioaiiy ni?eeiyoeeaino? iiiiioeeaa??a ia?eoa??eii?
e?ia? iieio?ieia?/ieo oai?eo aei aeciaaiiiai ?OI noi?iaiaeaeo?oueny
cieaeaiiyi ooieoe?iiaeueii? aeoeaiino? i?e?iaeieo ee?oei-e?ea??a oa
i?aeaeuaiiyi ??ai?a ?OI aaiia a ne?iaaooe? oeeo oai?eo. I?aeneeaiiy
oeeoie?oe/ii? aeoeaiino? e?ioioeeo?a, anioe?eiaaieo c iooeeiaie, i?e
?ieoaaoe?? oeeo ee?oei c ?OI aeueoa noi?iaiaeaeo?oueny ca?eueoaiiyi
aeoeaiino? 2-5A neioaoace.

3.Iaea?aeaii na??th ia?auaiethaaieo ee?oeiieo e?i?e ieoa/eo e?ioii, ye?
iiaeooue neoaoaaoe ca iiaeaeue aeey iaeii/aniiai aea/aiiy aieeao
oaeoi??a, ui iiaeoeththoue ae?th ?OI, ia i?ie?oa?aoe?th ee?oei oa
?ai?iaeoeoe?th ?ioaa?iaaieo ?ao?ia??on?a.

4.Iieacaii, ui a aacee?oeiieo nenoaiao i/euai? i?aia?aoe i?e?iaeieo o?IE
iiaeooue i?aaeoe ca aeoeaaoi?e 2-5A neioaoace cai?noue ooo/ieo
aeoeaaoi??a — aee?IE, ui aeicaiey? ia?aaeaa/aoe iiaeeeaino? oaeiai
ooieoe?iioaaiiy o?IE ? a i?e?iaeieo oiiaao.

5.Aeiaaaeaii, ui ?aoeii?aee iiaeooue ca iaaieo oiia aooe ?iaeoeoi?aie
?OI. ?ieoaaoe?y c ?aoeii?aeaie i?ecaiaeeea aei iii?oiiai aaeueioaaiiy
?inoo ee?oei ia?auaiethaaieo e?i?e ieoa/eo e?ioii oa aei nooo?aiai
cieaeaiiy ?ioaeoe?eiiai oeo?o A?E. Iieacaii, ui aoaeoe iiaeoethaaiiy
ae?? ?OI ?aoeii?aeaie a ia?aeiieo oa ia?auaiethaaieo eoeueoo?ao
iooeeiieo ee?oei iiaeooue iiina?aaeeiaoaaoenue /a?ac nenoaio 2-5A.

6.Iieacieee aeoeaiino? 2-5A neioaoace, eeth/iaiai oa?iaioo nenoaie ?OI,
iiaeooue aeei?enoiaoaaoenue aeey aecia/aiiy ni?eeiyoeeaino? ee?oei aei
?OI oa iiaeoeyoe?? ae?? ?OI i?ae aieeaii ?aoeii?ae?a.

Ia?ae?e iaoeiaeo i?aoeue, iioae?eiaaieo ca oaiith aeena?oaoe??

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1991. — O. 7, ?6. — N. 102-106

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?aeiiaeiaioiiai eioa?oa?iia ia eiaeoeoeeth 2,5-ieeaiaaeaieeaoneioaoacu a
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iaoeiaiai oiaa?enoaa o?ieia?a Oe?a?ie. -Ee?a. — 1993. — N. 278-279.

Verkhatskaya A.A., Zavelevich M.P., Grigorenko V.N., Khaetsky I.K.
Effects of retinoic acid on response of bladder cancer cells to
interferon // Abstracts of the 19th International Congress of
Chemotherapy. — Canada. — July 16-21, 1995. — P. 317

Aa?oaoeueea A., Caaaeaae/ I., ?eaaeei N., Ii??aiyeueia aea/aiiy i?io?e?a
2,5-ie?aiaaeai?eao?a o iiiiioeeaa?ao ia?eoa??eii? e?ia? oai?eo ia
aaiaoeo A oa ia NI?Ae // Ca??iee oac ia?oi? Iaoe?iiaeueii?
iaoeiai-i?aeoe/ii? eiioa?aioe?? c i?iaeai A?E/NI?Ae c i?aeia?iaeiith
o/anoth. Ee?a. — 24-26 n?/iy 1995. — N. 48-49

AIIOAOe?ss

Caaaeaae/ I.I. Nenoaia 2-5 ie?aiaaeai?eaoo a iooeeiieo oa
a??on?io?eiaaieo ee?oeiao i?e ae?? ?ioa?oa?ii?a oa ?? iiaeoeyoe?y
?aoeii?aeaie. — ?oeiien.

Aeena?oaoe?y ia caeiaoooy iaoeiaiai nooiaiy eaiaeeaeaoa a?ieia?/ieo iaoe
ca niaoe?aeuei?noth 14.01.07 — iieieia?y. — ?inoeooo aenia?eiaioaeueii?
iaoieia??, iieieia?? ? ?aae?ia?ieia?? ?i. ?.?.Eaaaoeueeiai IAI Oe?a?ie,
Oe?a?inueeee iaoeiai-aeine?aeiee ?inoeooo iieieia?? ? ?aae?ieia?? IIC
Oe?a?ie, Ee?a, 1999.

Aeena?oaoe?th i?enay/aii ieoaiiyi ooieoe?iioaaiiy
2(5(-ie?aiaaeai?eaoneioaoace, eeth/iaiai oa?iaioo nenoaie ?ioa?oa?iio, a
ia?auaiethaaieo e?i?yo oa ia?aeiieo eoeueoo?ao iooeeiieo ee?oei oa a
aoaeoi?ieo ee?oeiao ?ioiii? nenoaie oai?eo ia ?ae ie?ee oa ?ae na/iaiai
i?oo?a. I?iaiae?ciaaii ni?eeiyoeea?noue oeeo ee?oei aei ?ioa?oa?ii?a ca
aecia/aiiyi aeoeaiino? oeueiai oa?iaioo. Anoaiiaeaii, ui iiaeoeyoe?y
ae?? ?ioa?oa?ii?a ?aoeii?aeaie a iooeeiieo ee?oeiao iiaea
iiina?aaeeiaoaaoenue /a?ac nenoaio 2(5(-ie?aiaaeai?eaoo. Iaea?aeaii
ia?auaiethaai? e?i?? ee?oei ieoa/i? e?ioiie oa ioa?aeoa?eciaaii
anioe?eiaai? c ieie ?ao?ia??one. I?e aiae?c? ooieoe?iioaaiiy
2(5(-ie?aiaaeai?eaoneioaoace a aacee?oeiieo nenoaiao iieacaii, ui
i?aia?aoe i?e?iaeieo o?IE iiaeooue i?aaeoe ca ?? aeoeaaoi?e.

Eeth/ia? neiaa: ?ioa?oa?ii, 2(5(-ie?aiaaeai?eaoneioaoaca, ?ae ie?ee, ?ae
na/iaiai i?oo?a, eoeueoo?e iooeeiieo ee?oei, ia?auaiethaai? e?i??
e?ioii, ?aoeii?aee, o?IE

AIIIOAOeEss

Caaaeaae/ I.I. Nenoaia 2-5 ieeaiaaeaieeaoa a iiooieaauo e
ae?oneioeoee?iaaiiuo eeaoeao i?e aeaenoaee eioa?oa?iiia e aai
iiaeoeyoeey ?aoeiieaeaie. — ?oeiienue.

Aeenna?oaoeey ia nieneaiea o/aiie noaiaie eaiaeeaeaoa aeieiae/aneeo iaoe
ii niaoeeaeueiinoe 14.01.07 — iieieiaey. — Einoeooo yenia?eiaioaeueiie
iaoieiaee, iieieiaee e ?aaeeiaeieiaee ei. ?.A.Eaaaoeeiai IAI Oe?aeiu,
Oe?aeineee iao/ii-enneaaeiaaoaeueneee einoeooo iieieiaee e ?aaeeieiaee
IC Oe?aeiu, Eeaa, 1999.

Aeenna?oaoeey iinayuaia aii?inai ooieoeeiie?iaaiey
2(5(-ieeaiaaeaieeaoneioaoacu, eeth/aaiai oa?iaioa nenoaiu eioa?oa?iia, a
eoeueoo?ao ia?aaeaaaiuo eeiee, a ia?ae/iuo eoeueoo?ao iiiiioeeaa?ia
ia?eoa?e/aneie e?iae caei?iauo aeiii?ia e aieueiuo ae?oniui aaiaoeoii A,
a ia?ae/iuo eoeueoo?ao iiooieaauo eeaoie e iiiiioeeaa?ia ia?eoa?e/aneie
e?iae aieueiuo ?aeii ii/ee e ?aeii ii/aaiai iocu?y, a oaeaea a
eoeueoo?ao eeioioeeoia, eioeeueo?e?othueo ?aeiaua iiooiee ii/ee, iinea
eo au?aueaaiey in vitro c eioa?eaeeeiii-2. I?iaaaeaii n?aaieoaeueiia
eco/aiea niioiioaiee iaaeaeo enoiaeiuie e eiaeooee?iaaiiuie o?iaiyie
aeoeaiinoe neioaoacu e i?iaiaeece?iaaia /oanoaeoaeueiinoue enneaaeoaiuo
eeaoie e eioa?oa?iiai ii ii?aaeaeaieth aeoeaiinoe yoiai oa?iaioa.
Iieacaii, /oi eeaoee ia?ae/iuo eoeueoo? ?aea ii/ee e ?aea ii/aaiai
iocu?y a aieueoeinoaa neo/aaa auee aini?eei/eau e aeaenoaeth
?aeiiaeiaioiuo eioa?oa?iiia. Eiaeooee?iaaiiua o?iaie aeoeaiinoe
2(5(-ieeaiaaeaieeaoneioaoacu a iiiiioeeaa?ao ia?eoa?e/aneie e?iae
iieieiae/aneeo aieueiuo auee ieaea oaeiauo o caei?iauo ethaeae, a
iiiiioeeaa?u ia?eoa?e/aneie e?iae cia/eoaeueiie /anoe aieueiuo ae?oniui
aaiaoeoii A n iiauoaiiuie enoiaeiuie cia/aieyie aeoeaiinoe oa?iaioa auee
?ao?aeoa?iuie e aeaenoaeth eioa?oa?iia. Enoiaeiua o?iaie aeoeaiinoe
neioaoacu a eeaoeao ia?aaeaaaiuo eeioiaeanoieaeiuo eeiee auee
nouanoaaiii auoa a n?aaiaiee n oaeiauie eae a iiiiioeeaa?ao
ia?eoa?e/aneie e?iae, oae e a eeaoeao ia?ae/iuo eoeueoo? ?aea ii/ee e
?aea ii/aaiai iocu?y. Aianoa n oai, i?e aeaenoaee eioa?oa?iiia, a
iniaaiiinoe eioa?oa?iia aeueoa, ioia/aaony cia/eoaeueiia oaaee/aiea
o?iaiae aeoeaiinoe 2(5(-ieeaiaaeaieeaoneioaoacu, nouanoaaiii
i?aauoathuaa oaeiaia a ia?ae/iuo eoeueoo?ao iiooieaauo eeaoie.

Iieacaii, /oi nieaeaiea /oanoaeoaeueiinoe iiiiioeeaa?ia ia?eoa?e/aneie
e?iae aieueiuo ?aeii ii/aaiai iocu?y e eioa?oa?iiai nii?iaiaeaeaaony
nieaeaieai ooieoeeiiaeueiie aeoeaiinoe i?e?iaeiuo eeaoie-eeeea?ia yoeo
aieueiuo, /oi i?ienoiaeeo ia oiia iiauoaiey oeo?ia eioa?oa?iia aaiia a
nuai?ioea e?iae. I?e yoii oeo?u eioa?oa?iia aeueoa inoathony i?aeoe/anee
iaeciaiiuie. Eieoaaoeey i?e?iaeiuo eeaoie-eeeea?ia iieio?ieiae/aneeo
aieueiuo n eioa?oa?iiii aeueoa i?eaiaeeo e /anoe/iiio ainnoaiiaeaieth
iieacaoaeae eo ooieoeeiiaeueiie aeoeaiinoe. Oneeaiea oeeoieeoe/aneie
aeoeaiinoe eeioioeeoia, eioeeueo?e?othueo iiooiee, i?e aeaenoaee
eioa?oa?iia nii?iaiaeaeaaony iiauoaieai o?iaiae eiaeooee?iaaiiie
aeoeaiinoe 2(5(-ieeaiaaeaieeaoneioaoacu.

Onoaiiaeaii, /oi iiaeoeyoeey aeaenoaey eioa?oa?iiia ?aoeiieaeaie a
ia?ae/iuo eoeueoo?ao e ia?aaeaaaiuo eeieyo iiooieaauo eeaoie iiaeao
/anoe/ii inouanoaeyoueny /a?ac nenoaio 2(5(-ieeaiaaeaieeaoa.
I?aaeia?aaioea eeaoie ia?aaeaaaiuo eeiee ?aoeiiaaie eeneioie i?eaiaeeo e
cia/eoaeueiiio oneeaieth eiaeoeoeee a ieo neioaoacu i?e iineaaeothuae
eieoaaoeee n eioa?oa?iiii aeueoa. Oneeaiea eiaeoeoeee neioaoacu i?e
aeaenoaee eioa?oa?iia ioia/aaony e a iaeioi?uo ia?ae/iuo eoeueoo?ao
eeaoie ?aea ii/aaiai iocu?y i?e eo eieoaaoeee n ?aoeiiaaie eeneioie.
Eieoaaoeey eeaoie ia?aaeaaaiuo eeiee eeioii n ?aoeiieaeaie i?eaiaeeo e
nouanoaaiiiio caiaaeeaieth eo i?ieeoa?aoeee e i?e ii?aaeaeaiiuo oneiaeyo
— e eiaeae?iaaieth i?iaeoeoeee yiaeiaaiiuo ?ao?iae?onia. Eieoaaoeey
eioeoee?iaaiiuo eeaoie n ?aoeiieaeaie i?eaiaeeo e nouanoaaiiiio
nieaeaieth eioaeoeeiiiiai oeo?a ae?ona eiioiiaeaoeoeeoa /aeiaaea a
nenoaiao ino?ie e o?iie/aneie eioaeoeee eeioiaeanoieaeiuo eeaoie in
vitro.

I?e aiaeeca ooieoeeiie?iaaiey 2(5(-ieeaiaaeaieeaoneioaoacu a
aaneeaoi/iuo nenoaiao iieacaii, /oi i?aia?aou o?IE iiaoo neoaeeoue a
ea/anoaa aa aeoeaaoi?ia a aaneeaoi/iuo nenoaiao.

Eeth/aaua neiaa: eioa?oa?ii, 2(5(-ieeaiaaeaieeaoneioaoaca, ?ae ii/ee,
?ae ii/aaiai iocu?y, eoeueoo?u iiooieaauo eeaoie, ?aoeiieaeu, o?IE

SUMMARY

Zavelevich M.P. Effects of interferons on the state of 2-5
olygoadenylate system in cancer cells and virus-infected cells and
modulation of these effects by retinoids. — Manuscript.

Thesis for a candidate’s degree by speciality 14.01.07 — oncology.-
R.E.Kavetsky Institute of experimental pathology, oncology and
radiobiology, National Academy of Sciences of Ukraine, Ukranian Research
Institute of Oncology and Radiology Ministry of Health Care of Ukraine,
Kyiv, 1999.

The dissertation deals with the problems of the 2(5( oligoadenylate
synthetase functions in transplantable cell lines, primary cultures of
cancer cells and effector cells of immune system of renal cell carcinoma
and bladder cancer patients. The susceptibility of the cells under study
to interferons has been analysed in vitro by the 2(5( oligoadenylate
synthetase assay. The modulation of interferon effects by retinoids in
cancer cells has been shown to be partially mediated by
2(5(-oligoadenylate system. Analysis of synthetase reaction products in
cell-free system suggested that natural tRNA could serve as the
activators of. 2(5( oligoadenylate synthetase

Key words: interferon, 2(5( oligoadenylate synthetase, renal cell
cancer, bladder cancer, cancer cell cultures, retinoids, tRNA

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