OA?E?ANUeEEE AeA?AEAAIEE OI?AA?NEOAO

IAEAA?IA ??EIA AIAOIE??AIA

OAeE: 577.122 / 123.5: 615.9: 667.281

AIEEA AeENIA?NIEO ACIAA?AIEE?A

IA A?INEIOAC IOEEA?IIAEO EENEIO ? A?EE?A

C O?AOOAAIIssI A?AeAeAEAIEO AOAEO?A

03.00.04 — a?io?i?y

A A O I ? A O A ? A O

aeena?oaoe?? ia caeiaoooy iaoeiaiai nooiaiy

eaiaeeaeaoa a?ieia?/ieo iaoe

Oa?e?a — 1999

Aeena?oaoe??th ? ?oeiien

?iaioa aeeiiaia o eaai?aoi??? i?iieneiai? oieneeieia?? Aea?aeaaiiai
i?aei?e?inoaa Oa?e?anueeee iaoeiai-aeine?aeiee ?inoeooo a?a??ie i?aoe?
oa i?iocaoai?thaaiue I?i?noa?noaa ioi?iie caei?ia’y Oe?a?ie

Iaoeiaee ea??aiee: aeieoi? a?ieia?/ieo iaoe, i?ioani?

Eeeiaiei Aiaoie?e ?aaiiae/,

Oa?e?anueeee aea?aeaaiee ?inoeooo
o?ce/ii? eoeueoo?e

I?i?noa?noaa ina?oe Oe?a?ie oa
Aea?aeaaiiai eii?oaoo

Oe?a?ie c o?ce/ii? eoeueoo?e oa
nii?oo,

caa?aeoaa/ eaoaae?e a?ieia?/ieo
iniia

o?ce/iiai aeoiaaiiy oa nii?oo.

Io?oe?ei? iiiiaioe: aeieoi? a?ieia?/ieo iaoe, i?ioani?

Eoaiaee Aieiaeeie? Eineiiae/,

?inoeooo i?iaeai e??ia?ieia?? ?

e??iiaaeeoeeie IAI Oe?a?ie (i.
Oa?e?a),

caa?aeoaa/ a?aeae?eo
e??ii?ioaeoi??a

aeieoi? a?ieia?/ieo iaoe

Eiyc?aa Ia?eia Aeaaeeneaa?aia,

Oa?e?anueeee ?inoeooo
oaeineiiaeaiiy e?ea??a IIC Oe?a?ie,

i?ioani? eaoaae?e ee?i?/ii?
a?io?i?? oa

noaeiai-iaaee/ii? oieneeieia??

I?ia?aeia onoaiiaa: ?inoeooo oa?iaeieia?? ? oieneeieia?? AII Oe?a?ie

(a?aeae?e a?io?i?/ii? oa?iaeieia??),
i. Ee?a

(??oaiiyi niaoe?aaee i?io. ? 2 a?ae
3.03.99 ?. ci?iaia ia

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

Iiiinoa?noaa inaioe Oe?a?ie (eaoaae?a
a?io?i??), i. Eueaia).

Caoeno a?aeaoaeaoueny “17 ” aa?aciy 1999 ?. i 1515 aiaeei? ia
can?aeaii? niaoe?ae?ciaaii? a/aii? ?aaee E 64.051.17 i?e
Oa?e?anueeiio aea?aeaaiiio oi?aa?neoao? ca aae?anith:
310077, i. Oa?e?a, ieiua Naiaiaee, 4, aoae. 3-15

(??oaiiyi niaoe?aaee i?io. ? 2 a?ae 3.03.99 ?. caoeno ia?aianaii ia 21
ea?oiy 1999 ?)

C aeena?oaoe??th iiaeia iciaeiieoeny o Oeaio?aeuei?e iaoeia?e
a?ae?ioaoe? Oa?e?anueeiai aea?aeaaiiai oi?aa?neoaoo I?i?noa?noaa ina?oe
Oe?a?ie ca aae?anith: 310077, i. Oa?e?a, ieiua Naiaiaee, 4

Aaoi?aoa?ao ?ic?neaiee “_5_” ethoiai 1999 ?.

A/aiee nae?aoa? niaoe?ae?ciaaii?

a/aii? ?aaee, eaiaeeaeao a?ieia?/ieo iaoe
A.?. Iaaeaeei

CAAAEUeIA OA?AEOA?ENOEEA ?IAIOE

Aeooaeueiinoue oaie. Aea/aiiy aeeiai?ee a?ineioaco ioeea?iiaeo eeneio ?
a?ee?a, iaoai?ci?a oeeo i?ioean?a oa ?o ?aaoeyoe?? ? iaei??th c
ooiaeaiaioaeueieo i?iaeai a?io?i??. Inoaii?i /anii aeine?aeaeaiiy o oe?e
aaeoc? aoei ni?yiiaaii ianaiia?aae ia aea/aiiy a?ineioaco AeIE, ?IE ?
a?ee?a o ii?iaeueieo ee?oeiao oaa?ei ca ??ciiai o?c?ieia?/iiai noaio
(noa??iiy, caoaeaeaiiy oa ?io?) [E.TH.Oeeiaie e niaao., 1986;
A.E.Eeeiaiei e niaao., 1987, 1988, 1991; A.I.Eioa?ia, 1994, 1997; O.A.
Iicaeooeia e niaao., 1996, 1997; G.Almouzni, 1993]. Ia no/aniiio aoai?
?icaeoeo a?io?i?? aeooaeueieie ? aeine?aeaeaiiy iniaeeainoae ?o
a?ineioaco o ee?oeiao i?e ??cieo oi?iao iaoieia?? (iooeeiiee ??no,
a??oni? ?ioaeoe?? oa ?i.), a oaeiae ca oiia ae?? ?aae?aoe??, iooaaai?a
oa ?ioeo oaeoi??a. Oaea ci?ia ni?yiiaaiino? aeine?aeaeaiue coiiaeaia
c?inoaiiyi ?aaeueiiai iaaaioaaeaiiy ia i?aai?ci ethaeeie oe?aeeeaeo
/eiiee?a ??cii? i?e?iaee, ia?aaaaeii o?i?/ieo, aiane?aeie ?ioaineaiiai
caa?oaeiaiiy iaaeieeoiueiai na?aaeiaeua [TH.E.Aoanueeee e niaao, 1993;
A.I.Na?aethe, 1996]. Aeacai? iaaaoeai? yaeua nooo?ai a?aeaeaathoueny ia
iieacieeao caei?ia’y ianaeaiiy. Oae, a Oe?a?i? ca 1992-1997 ??.
ca?eueoeeany ia 16 % iieieia?/ia caoai?thaai?noue o?i?/ii? ao?ieia??.
Oea oaeiae noino?oueny ?yaeo ?ioeo caoai?thaaiue, ye? iia’ycai? c
iioeiaeaeaiiyi aaiaoe/ii? ?ioi?iaoe?? i?ae /an neioaco ee?oeiieo
eiiiiiaio?a, oiaoi niaaeeiaeo caoai?thaaiue, ii?ooaiue ?ai?iaeoeoeaii?
ooieoe??, oneeaaeiaiue ia?aa?ao aaa?oiino? [A.I. Na?aethe, 1997]. An?
oe? oi?ie iaoieia?? iae/ano?oa coiiaeai? ae??th ia i?aai?ci aaiaoe/ii
aeoeaieo /eiiee?a, o o./. enaiia?ioee?a. Na?aae inoaii?o cia/iee
a?aenioie neeaaeathoue o?i?/i? ?a/iaeie, ui iathoue iooaaaii?,
eaioea?iaaii?, aiiaaei- oa aia??io?iii? aeanoeaino? [?.?.Aa?eeye ?
ni?aaao., 1996; ?.A.Aii/a?oe ? ni?aaao., 1996].

A?aeiii, ui iieaeoey?iith iniiaith a?aeaeaeaieo iane?aee?a, iaoiiaeaieo
aieeaii enaiia?ioee?a, ? ii?ooaiiy no?oeoo?ii-ooieoe?iiaeueiiai noaio
aaiaoe/iiai aia?aoo ia ??cieo ??aiyo eiai i?aai?caoe??, aeeth/ath/e ?o
aca?iiae?th c AeIE, eiiiiiaioaie o?iiaoeiiaiai eiiieaeno oa yaea?iei
iao?eenii [O.A.Nuyenoa e niaao., 1991; F.Perera, 1991; A.Dipple, 1995].
?icaeoie a?aeaeaeaieo aoaeo?a noi?iaiaeaeo?oueny cia/iith ia?aaoaeiaith
iaoaaie?/ieo i?ioean?a o ee?oeiao, a ia?oith eaieith o nieao?ii? oaeeo
ia?aoai?aiue ? ii?ooaiiy iai?io ioeea?iiaeo eeneio, cie?aia ?o
a?ineioaco [E.O.Naeoe e niaao., 1986; I.A.Oea?oeeaeca, 1991;
A.I.Eaaiia e niaao., 1996; E. Lee et al., 1989; T. Boulikas, 1992].

Iaeiae, caeeoa?oueny iac’yniaaiei ieoaiiy, ye? naia ci?ie aeeiai?ee
i?ioean?a ?aie?eaoe?? oa o?aine?eioe?? iia’ycai? c eaioea?iaaiacii,
iooaaaiacii oa ?ioeie aaiaoe/ii coiiaeaieie aoaeoaie ca oiia ae?? ia
i?aai?ci enaiia?ioee?a.

Iaaeinoaoiuei aea/aiith ? oaeiae i?iaeaia iaoai?ci?a ii?ooaiue
neioaco AeIE ? ?IE i?ae aieeaii ??cieo o?i?/ieo ?a/iaei. Ci?ie
ooieoe?iiaeueii? aeoeaiino? yaea?iiai aia?aoo a cia/i?e i??? aieeaathoue
ia a?ineioac yaea?ieo a?ee?a, a ia?oo /a?ao a?noiiiaeo ? iaa?noiiiaeo
[N.I.Aieeeia e niaao., 1986; TH.E.Ieo?thoei e niaao., 1989;
A.E.Eeeiaiei e niaao., 1991]. Ci?ie aeeiai?ee a?ineioaco ioeea?iiaeo
eeneio ? a?ee?a, iaoai?cie ii?ooaiue oeeo i?ioean?a ca oiia ae?? ??cieo
eean?a aaiioiene/ieo o?i?/ieo niieoe iiaeooue iaoe ye caaaeuei?
caeiiii??iino?, oae ? iaaio niaoeeo?/i?noue. Oiio aea/aiiy a?ineioaco
AeIE, ?IE ? a?ee?a a oiiaao ae?? ??cieo enaiia?ioee?a, ye? caeaoi?
ni?e/eiyoe a?aeaeaeai? aoaeoe (iooaaaiiee, eaioea?iaaiiee
aiiaaeio?iiiee oa ?i.), ? aaeueie aeooaeueiei.

Iaei??th c iaea?eueo a?aeiieo a?oi aaiioiene/ieo eaioea?iaai?a ?
niieoee eeano ai?iiaciaaicie?a [H.Mori, 1990; K.Chung, 1992; IARC
monographs, 1991, 1993; P. Shubik, 1995], aei yeeo iaeaaeeoue ? iiaa,
i?aeoe/ii ua iaaea/aia a?oia enaiia?ioee?a — aeenia?ni? aciaa?aieee
(iio?aei? 4-i?o?i-4’-ai?iiaciaaicieo). Oe? niieoee, ye oaeoi?e ?eceeo
a?aeaeaeaieo aoaeo?a, noaiiaeyoue cia/iee iaoeiaee ?ioa?an o ieai?
aeine?aeaeaiiy ?o aieeao ia a?ineioac ioeea?iiaeo eeneio ? a?ee?a.

Ana aeua aeeeaaeaia cana?ae/o? aeooaeuei?noue i?iaaaeaiiy aeine?aeaeaiue
a?ineioaco ioeea?iiaeo eeneio ? yaea?ieo a?ee?a oa ioe?iee ca’yceo oeeo
i?ioean?a c a?aeaeaeaieie aoaeoaie i?ae /an iiaeaethaaiiy
eaioea?iaaiaco, iooaaaiaco oa ii?ooaiue nia?iaoiaaiaco, coiiaeaieo
aieeaii i?o?iai?iiaciaaicie?a. Aeine?aeaeaiiy o oeueiio iai?yieo
iathoue aaaeeeaa iaoeiaa cia/aiiy, c iaeiiai aieo, aeey c’ynoaaiiy
iaoiaaiaco oi?i caoai?thaaiue, iia’ycaieo c iioeiaeaeaiiyi aaiaoe/iiai
aia?aoo, a c ae?oaiai, aeey anoaiiaeaiiy caeiiii??iinoae aaiioiene/ii?
ae?? aeenia?nieo aciaa?aiee?a c eeano ai?iiaciaaicie?a.

Aeooaeuei?noue aeine?aeaeaiue aieeao aeenia?nieo aciaa?aiee?a (AeAA) ia
a?ineioac ioeea?iiaeo eeneio ? a?ee?a coiiaeaia ua e oei, ui c oeeie
niieoeaie eiioaeoothoue cia/i? eiioeiaaioe i?aoe?aiee?a, ui noai?th?
?aaeueio caa?ico i?ioan?eieo caoai?thaaiue [I.I.Eocueiaiei, 1986;
I.A.Aauoe, 1989; A.E.Noa?iaeoiia, 1991]. Oae? aeine?aeaeaiiy iathoue
aaaeeeaa cia/aiiy aeey ?ica’ycaiiy i?eeeaaeii? i?iaeaie ?ic?iaee
i?io?eaeoe/ieo caoiae?a — oaeineiiaeaiiy iaoeiai-iaoiaee/ieo iiaeoiae?a
aei aiai?ii/iiai ?aaeaiaiooaaiiy niieoe oeueiai eeano.

Ca’ycie ?iaioe c iaoeiaeie i?ia?aiaie oa oaiaie. Iaoa?iaeaie aeaii?
aeena?oaoeieii? ?iaioe ? ?acoeueoaoe aeineiaeaeaiue, iaea?aeaii aaoi?ii
i?ae /an aeeiiaiiy IAe? «Aea/aiiy oieneeiaeeiaiiee i iaa?oiooaaiiy
aiai?ii/ieo ?aaeaiaioia c o?aooaaiiyi aiaeaeaeaieo aoaeoia aeey
iiaeeaiaeoaeueieo i noiioieo ia?ie aeenia?nieo aciaa?aieeia», N
aea?aeaaii? ?a?no?aoei? 01. 90.0016.666.

Iaoa ?iaioe — aiaeic iniaeeainoae a?ineioaco oa ci?i e?euee?niiai ai?noo
ioeea?iiaeo eeneio (AeIE, ?IE) oa ??cieo eean?a yaea?ieo a?ee?a
(a?noiiiaeo, iaa?noiiiaeo, aeiaoe?iiaeo) i?ae aieeaii aeenia?nieo
aciaa?iee?a c o?aooaaiiyi a?aeaeaeaieo iane?aee?a oa i?iya?a oiene/ii?
ae??.

Caaaeaiiy aeineiaeaeaiiy:

1. Aea/eoe aieea ?yaeo AeAA ia aiineioac, eieueeiniee aiino oa
ni?aa?aeiioaiiy AeIE ? ?IE o yae?ao ee?oei ia/iiee, nii’yiee?a oa
einoeiaiai iiceo uo?ia in vivo ca oiia iaeii- oa naie?aciai?
ia?i?aeueii? ae??, a oaeiae o?ii?/ii? ?iaaeyoe??.

2. I?iaanoe aeine?aeaeaiiy iniaeeainoae a?ineioaco a?noiiiaeo,
iaa?noiiiaeo ? aeiaoe?iiaeo a?ee?a oa ci?i ?o eieueeiniiai aiinoo o
yae?ao ee?oei ia/?iee uo??a in vivo ca oiia iaeii?aciai? ia?i?aeueii?
ae?? oa o?ii?/ii? ?iaaeyoe?? ?yaeo AeAA.

3. Ioeiieoe oa?aeoa? ci?i e?euee?nieo ni?aa?aeiioaiue i?ae ioeea?iiaeie
eenei-oaie oa a?eeaie, oa i?ae ??cieie a?eeaie o ia/?ioe? uo??a i?ae
aieeaii ?yaeo AeAA.

4. Anoaiiaeoe ca’ycie ci?i a?ineioaco AeIE, ?IE ? a?ee?a c a?aeaeaeaieie
aoaeoaie (iooaaaiiei ? aiiaaeio?iiiei) oa i?iyaaie caaaeueiioiene/ii?
ae?? AeAA.

5. Ia i?aenoaa? io?eiaieo ?acoeueoao?a aeine?aeaeaiue iaa?oiooaaoe
aiai?ii/ii ?aaeaiaioe o iiaio?i ?iai/i? ciie aeey aea/aieo aeenia?nieo
aciaa?aieeia.

Iaoeiaa iiaecia i oai?aoe/ia cia/ouinoue ?iaioe.

1. Io?eiai? aeai? c a?io?i?? iiaiai eeano enaiia?ioee?a — aeenia?nieo
aciaa?aiee?a ye? iaeaaeaoue aei a?oie i?iieneiaeo io?oo ? ?
/oaei??aeieie aeey ii?iaeueieo iaoaaie?/ieo oeyo?a i?aai?cio. Aia?oa
aea/ai? iniaeeaino? a?ineioaco ioeea?iiaeo eeneio oa ??cieo eean?a
a?ee?a, ci?ie ?o e?euee?niiai ai?noo oa ni?aa?aeiioaiue i?ae ieie a
yae?ao ee?oei ??cieo i?aai?a ca oiiae ae?? AeAA. Anoaiiaeaii, ui
oa?aeoa? oa nooi?iue ae?aaeaiino? aeacaieo i?ioean?a caeaaeaoue a?ae
aeice, oeyoo oa e?aoiino? aaaaeaiiy, /ano aeniiceoe??, a oaeiae
iniaeeainoae iaoaaie?cio o aeine?aeaeaiiio i?aai?. Ia oii? oeeo ci?i
aia?oa aeine?aeaeai? iiaeeea? a?aeaeaeai? iane?aeee iioeiaeaeoth/iai
aieeao oeeo niieoe ia i?aai?ci, a oaeiae i?iyae ?o caaaeueiioiene/ii?
ae??.

2. Iieacaii, ui iaeiei c iaoaiici?a, ui aecia/athoue aaiioiene/iee, a
oaeiae eaioea?iaaiiee aoaeo ai?iiaciaaicie?a, ? ci?ie (ia?aaaaeii
aaeueioaaiiy) aiineioaco AeIE, a?noiiiaeo oa iaa?noiiiaeo a?ee?a o
yae?ao ee?oei i?aai?a-i?oaiae (ia/?iee oa n?i’yiee?a). Aaeueioaaiiy
a?ineioaco AeIE, a oaeiae aaiaoe/i? iioeiaeaeaiiy o noaoaaeo ee?oeiao
naioe?a iiaeooue aooe iaeiei c iaoai?ci?a ii?ooaiiy ?ai?iaeoeoeaii?
ooieoe?? oaa?ei. Anoaiiaeaii, ui aieiaiei aeaiaioii iaoaiicio
caaaeueiioiene/ii? aei? AeAA ? ?o iioeiaeaeoth/ee aieea ia a?eo?ioeeoe
ca ?aooiie caeaoiinoi iiaeoeaoaaoe aaiiaeiaii a iao- i noeueoaaiiaeiaii
c iiaeaeueoei ooai?aiiyi oieaoeue Aaeioey i ?icaeoeii aaiieioe/ii?
aiaii?.

3. Iaa?oioiaaii eiiieaen i??i?eoaoieo aeiaaiinoe/ieo e?eoa?i?a aeey
ioe?iee aea??eiaino? iioeiaeaeoth/i? ae?? AeAA ia i?aai?ci, yeee iiaea
aooe aeei?enoaiee c iaoith aiai?ii/iiai ?aaeaiaiooaaiiy niieoe eeano
AeAA.

I?aeoe/ia cia/ouinoue ?iaioe.

1. ?aeiiaiaeiaaii aenia?eiaioaeueii iaa?oioiaaiee iaoiaee/iee iiaeoiae
aei aiai?ii/iiai ?aaeaiaiooaaiiy niieoe eeano AeAA, caniiaaiee ia
aeyaeaiii ci?i a?ineioaco ioeea?iiaeo eeneio oa yaea?ieo a?ee?a,
niaoeeoi/ieo aiaeaeaeaieo aoaeoia (iooaaaiiiai ? aiiaaeio?iiiiai) ye
i?ii?eoaoieo e?eoa?i?a ioeiiee ?o iioeiaeaeoth/i? aei? ia i?aaiici.

2. Aenia?eiaioaeueii iaa?oioiaai? a?aie/ii aeiionoei? eiioeaio?aoe??
(AAeE) o iiaio?i ?iai/i? ciie aeey 4 aciaa?aieeia: *a?aiii-ei?e/iaaiai
AE (Ae*E-AE), *a?aiiiai AE (Ae*-AE), Oaiii-neiueiai C (AeON-3) i
*a?aiiiai 2N (Ae*-2N) aeicaieythoue caeienithaaoe ia?aaiaeiee i
iiia?aaeaeoth/ee naiioa?iee iaaeyae ca aiinoii oeeo aa?aieeia o iiaio?i
ae?iaie/eo i?eiiuaiue, ui ? aaaeeeaei i?io?eaeoe/iei caoiaeii.

3. Iaea?aeai? a?io?i?/i?, aaiaoe/i? oa oieneeieia?/i? aeai? aiieiai/ii?
aei? AeAA aeei?enoaii i?e neeaaeaiii i?ioieaeoe/ieo ?aeiiaiaeaoeie,
ni?yiiaaieo ia iioeiicaoeith oiia i?aoei ? iiia?aaeaeaiiy ?icaeoeo
i?ioanieieo caoai?thaaiue i?aoe?aiee?a aiaeiiaiaeieo ae?iaieoeoa.

4. ?acoeueoaoe aeine?aeaeaiue iniaeeainoae a?ineioaco
ioeea?iiaeo eeneio ? a?ee?a i?ae aieeaii AeAA iathoue aaaeeeaa cia/aiiy
aeey ?ic?iaee aoaeoeaieo aioeeaioea?iaaiieo i?aia?ao?a, iaoai?ci ae??
yeeo caniiaaiee ia aeieoaaii? neioaco AeIE oa a?ee?a o yae?ao iooeeiieo
ee?oei.

Ai?iaaaeaeaiiy ?acoeueoao?a aeine?aeaeaiiy aei i?aeoeee.

1. Aeai? i?i aaiioiene/io ? aiiaaeio?iiio iaaaciaeo aea/aieo AeAA
aeei?enoaii aeey neeaaeaiiy ii?iaoeaii-oaoi?/ii? aeieoiaioaoe?? ia oe?
o?i?/i? niieoee oa oaoiieia?/i? i?ioeane oeyoii aeeth/aiiy o ?icae?ee
“Aeiiae aaciaee oa ioi?iie iaaeieeoiueiai na?aaeiaeua” (1994 ?.). Oe?
aeiiae aoei ai?iaaaeaeaii ia i?aei?e?inoaao ai?e?iioa?aiai? aaeoc?
i?iieneiaino? Oe?a?ie.

2. A?aeiiino? i?i iniaeeaino? a?ieia?/ii? ae?? aea/aieo AeAA aeeth/aii
aei aaieo aeaieo ?a?no?o iioaioe?eii oiene/ieo oa iaaacia/ieo o?i?/ieo
?a/iaei ?O.

3.Aeey i?io?eaeoeee i?ioan?eieo caoai?thaaiue o ae?iaieoeoa? aeenia?nieo
aciaa?aiee?a aenia?eiaioaeueii iaa?oioiaai? aaee/eie AAeE o iia?o??
?iai/i? ciie, ye? caoaa?aeaeai? oa aeeth/ai? o aeiiiaiaiiy ? 4 aei
ia?ae?eo AAeE (a?ae 15.11.1989) aeey Ae*-2N, ? 8 aeey Ae*-AE ? AeON-C
(a?ae 1.06.1993) oa ? 9 (a?ae 1.01.1994) aeey Ae*E-AE.

Iniaenoee aianie aeena?oaioa a io?eiai? iaoeia? ?acoeueoaoe.

Aaoi? iniaenoi i?ia?a ?ioi?iaoe?eiee iiooe oa e?eoe/ii ioe?iea iayaio
e?oa?aoo?o ca oaiith aeine?aeaeaiiy, aecia/ea iaoo oa caaaeaiiy
aeine?aeaeaiue, oeyoe ?o ?ica’ycaiiy. Aaoi?ii iniaenoi oa ca eiai
aaciina?aaeiueith o/anoth aeeiiai? an? aoaie aenia?eiaioaeueieo
aeine?aeaeaiue iniaeeainoae a?ineioaco AeIE, ?IE oa yaea?ieo a?ee?a a
??cieo i?aaiao i?ae aieeaii AeAA, a oaeiae a?aeaeaeaieo iane?aee?a oa
i?iya?a oiene/ii? ae?? oeeo niieoe. Aaoi?ii iniaenoi aeeiiaii
noaoenoe/io ia?iaeo iaea?aeaieo ?acoeueoao?a, iniaenoi oa o ni?ai?aoe? c
iaoeiaei ea??aieeii i?iaiae?ciaai? ?acoeueoaoe aeine?aeaeaiue. Aea/aiiy
iooaaaiiiai (iaoiaeii aeii?iaioieo eaoaeueieo iooaoe?e) ?
aiiaaeioiene/iiai aoaeoia cae?eniaii c o/anoth iaoe. ni?a?ia.
eaai?aoi??? i?iioieneeieia?? AeI Oa?e?anueeee IAe? a?a??ie i?aoe? oa
i?iocaoai?thaaiue Ae.I.Aeaaaeein. Eiinoeueoaoeaia aeiiiiiaa a
?ioa?i?aoaoe?? ?acoeueoao?a oieneeieia?/ieo aeine?aeaeaiue iiaeaia
i?ia?aeiei iaoeiaei ni?a?ia?oieeii eaai?aoi??? i?iioieneeieia??
icia/aiiai i?aei?e?inoaa, eaiae. iaae. iaoe A.?. Caacaeae.

Ai?iaaoeiy ?acoeueoaoia aeena?oaoei?. Iaoa?iaee aeena?oaoei? aoee
i?aaenoaaeaii i iaaiai?aii ia eiioa?aioei? iieiaeeo a/aieo
Oa?eianueeiai IAeI aiai?ie i?aoei i i?iocaoai?thaaiue (1989, 1993, 1994,
1997), iiaeia?iaeiiio neiiicioii «I?iaeaie oieneeieiai? i i?eeeaaeii?
aeieiai?» (Iineaa-Ia?iue, 1991), caniaeaiii Oa?eianueeiai aiaeaeieaiiy
Oe?a?inueeiai oiaa?enoaa oa?iaeieiaia i oieneeieiaia (1992), caniaeaiii
naeoei? «I?iioieneeieiaiy» i?e i?iaeaiiie eiiini? «Iaoeiai iniiae
aiai?ie i?aoei i i?ioiaoieiai?» (Iineaa, 1993), eiioa?aioei? aei
100-?i//y c aeiy ia?iaeaeaiiy I.I. *a?eana «Oeiea aeaae. I.*a?eana:
iaea?, ?icaeoie, ia?niaeoeaa» (Ee?a, 1994), II c’?caei iaaee/ieo
aaiaoeeia Oe?a?ie (Eueaia, 1995), iaoeiiiaeueiiio c’?caei aiai?iinoia
Oe?a?ie (Ee?a, 1997), 1 Iiaeia?iaeiiio iaaee/iiio Eiia?ani nooaeaioia i
iieiaeeo a/aieo (Oa?iiiieue, 1997), i?aeia?iaeiiio neiiicioii
«Aacieiaeaey. Aeiiiiiaeii ?ai?iaeoeoeaii oaoiieiai?» (Ee?a, 1997),
iaoeia?e eiioa?aioe?? “Aeooaeuei? i?iaeaie a?a??ie i?aoe? ?
i?ioiaoieia?? a iaoeiiaoaeoaaii? oa o?i?/i?e i?iieneiaino?” (Oa?e?a,
1998).

Ioaeieaoei?. Ca iaoa?iaeaie aeena?oaoei? iioaeieiaaii 22 iaoeiai ?iaioe
(c yeeo 7 naiinoieii), a oiio /enei: 9 noaoae o iaoeiaeo aeo?iaeao, 4
noaooi o cai?ieeao iaoeiaeo i?aoeue, 9 ?iaio o iaoa?iaeao i oacao
eiioa?aioeie.

No?oeoo?a oa ianya aeena?oaoe??. Aeena?oaoeiy neeaaea?oueny c?
anooio, iaeyaeo eioa?aoo?e (?icaeie 1), aeeeaaeaiiy i iaaiai?aiiy
aeanieo aeineiaeaeaiue, aeeth/ath/e iaoiaee/io /anoeio (?icaeiee 2-7),
caeeth/aiiy, aeniiaeia, nieneo eioa?aoo?e i aeiaeaoeo. Ianya
aeena?oaoei? — 150 noi?iiie, a oiio /enei 13 iaethieia — 13 noi?., 18
oaaeeoeue (3 — ca oaenoii, 15 — o aeiaeaoeo) — 22 noi?., nienie
aeei?enoaii? eioa?aoo?e (196 aeaea?ae: 107 aio/eciyieo oa e?a?i NIAe i
89 ?iicaiieo) — 16 noi?., aeiaeaoie A — 18 noi??iie.

IAOA?IAEE I IAOIAeE AeINEIAeAEAIUe

A ?iaioi aeei?enoaii 1194 noaoaaic?ieeo a?eeo uo?ia iaio noaoae
iiioeyoe?? A?noa? ? 102 iaeiiieii aiei ieoi. A aenia?eiaioaeueieo
aeine?aeaeaiiyo oaa?eie caciaaaee aieeao aciaa?aieeia Ae*E-AE, Ae*-2N,
AeON-3, Ae*-AE, AeI-2E i Ae? (iioiaeieo 4-iio?i-4′-aiiiiaciaaicieo).
Oe? niieoee a?ae??ciythoueny i?ae niaith i?e?iaeith cai?niee?a o
aaicieueieo e?eueoeyo (a?ii-, oei?, oe?ai-, aoeaoai?ii-, iaoiene-) oa ii
ai?iia?oi? (aoee-, oe?aiaoee-, ieneaoee-, aoeaoieneaoee-,
i?ii?iieeieneaoee-).

Aieea AeAA ia iniaeeaino? a?ineioaco ? eieueeiniiai aiinoo AeIE ?
?IE, ainoiiiaeo (AA), iaainoiiiaeo (IAA) i aeiaoeiiiaeo (AeA) a?ee?a
yaea? aeine?aeaeaii a ia/iioei, nii’yieeao oa einoeiaiio iiceo
uo?ia-naioeia o o?ueio iacaeaaeieo iinoaiiaeao aenia?eiaio?a in vivo:
ca oiia ei?ioei/anii? ae?? AeAA, oiaoi ia?i?aeueiiai iaeii?aciaiai
aaaaeaiiy AeON-C, Ae*-2N, AeI-2E ? Ae? (5 a/ea) i Ae*E-AE (1,61
a/ea = 1/2 DL50) oa 7-?aciaiai aaaaeaiiy AeI-2E (1 a/ea) ? Ae*E-AE
(0,32 a/ea = 1/10 DL50), a oaeiae a oiiaao o?iii/ii? iiaaeyoei? Ae*E-AE
(2,5 ? 4 i?nyoe?; 25,4 ? 5,3 ia/i3). sse iiceoeaiee eiio?ieue
aeei?enoiaoaaeinue aaaaeaiiy aoaeiiiiai iooaaaio oeeeeioinoai?aeo.
Oaa?ei aeaeai?ooaaee /a?ac 6, 24 ? 48 aiae. i?ney inoaiiueiai aaaaeaiiy
niieoe

C iaoith aea/aiiy a?ineioaco AeIE ? ?IE uo?ai ca 2 aiaeeie aei caaith, a
aeey aea/aiiy a?ineioaco a?eea — ca 1 aiaeeio aaiaeeee a /a?aaio
ii?iaeieio i?/ai? iiia?aaeieee: 3I-o?i?ae?i (2 Iae/100 a i.o.),
3I-o??ae?i (1 IAe/100 a i.o.) ? 14N-ai?iieeneioe a?ae?ie?caoo a?ee?a
oei?aee (1 IAe/100 a i.o.). ssae?a c aiiiaaiaoo aeine?aeaeaieo i?aai?a
aeae?eyee iaoiaeii aeeoa?aioe?eiiai oeaio?eooaoaaiiy o 0,25 I ? 0,31 I
?ic/eiao naoa?ice c aeiaaaeith MgCl2o6H2O ? o??n-HCl [Chauveau J. et
all., 1956]. Eiioeaio?aoeith AeIE i ?IE aecia/aee ca iaoiaeii
Ae.Oiiaeoa i N.Oaiiaaoca?a a iiaeeoieaoei? I.A.O?oaeiethaiai? [1977] oa
niaeo?ioioiiao?e/ii [A.N.Nie??i, 1960]. Aeiaoe?iiao o?aeoe?th yaea?ieo
a?ee?a io?eioaaee a i?ioean? i?iieaee yaea? 0,14 I ?ic/eiii NaCl ?
oeaio?eooaoaaiiy i?e 2500 g. A?noiiiao o?aeoe?th a?ee?a c inaae?a
i?aia?ao?a yaea? io?eioaaee aeno?aeoe??th ca aeiiiiiaith 0,25 N HNl ?
iiaeaeueoei oeaio?eooaoaaiiyi i?e 2500 g. Aeno?aeoe?th IAA c i?aia?ao?a
yaea? i?iaiaeeee o 0,1 N NaOH, aeae? a?eeiaee aeno?aeo a?aeae?eyee
oeaio?eooaoaaiiyi (2500 g). Eiioeaio?aoe?th AeA ? AA aecia/aee ii
iioe/i?e u?eueiino? i?e aeiaaeei? oaee? 280 ii ia niaeo?ioioiiao??
NO-46; IAA — ca iaoiaeii Ae. Eio?i oa niiaaao. [1951] oa
niaeo?ioioiiao?e/ii i?e aeaio oaeeyo 260 ? 280 ii [A.A. Ei/aoeia, 1980]
c iiia?aaei?i ?o ia?ainaaeaeoaaiiyi o 5 % o?eoei?ioeoia?e eeneio?.

Iioaineaiinoue aiineioaco AeIE, PIE i aieeia aecia/aee ?aaeiiicioiiiei
?iaeeiii-noeeioeeyoeieiei iaoiaeii [N.A.Inoa?iai, 1983; ?oe-ai AIC ii
ENO, 1989]. ?aae?iaeoeai?noue o i?iaao aei??thaaee ia e?/eeueieeo Aaoa-I
o ??aeeiiiio noeeioeeyoi??, yeee i?noeoue ia e?o? ae?ienaio 100 a
iaooae?io, 5 a 2,5-ae?oai?eienacieo ? 250 ia
1,4-ae?-5-oai?e-2-ienacie?eaaicieo. O oeaeii aeey ?aooaaiiy aiineee 0,5
ie i?iae oa 15 ie noeeioeeyoi?a.

Iooaaaiia aeoeaiinoue AeAA aea/aeany a nenoaii ei?ioei/anieo
oanoia (E*O): oanoi Aeina [E.I.Oiiooaei i niiaaao.,1985],
oeeoiaaiaoe/iei iaoiaeii (o?aooaaiiy /anoioe o?iiiniiieo aaa?aoeie (OA)
a eeioeiao einoeiaiai iiceo uo?ia in vivo) i oano? ia ?iaeoeoe?th
/anoioe aeiiiiaioieo eaoaeueieo iooaoeie (AeEI) o uo??a-naioe?a [I.A.
Naiioeueeee oa niiaaao., 1978; ?oe-ai AIC ii ENO, 1989]. Oiene/iee
aieea aa?aieeia ia aiiaaee naioeia uo?ia aeineiaeaeoaaany c
aeei?enoaiiyi eiiieaena ooieoeiiiaeueieo i ii?oieiai/ieo iieacieeia
noaio nia?iaoiaaiaco, a oaeiae ii?oi-no?oeoo?iiai aiaeico nii’yieeia
[I.A. Naiioeueeee, 1979; I.I. Eeoaeiiaa, 1983].

Iniaeeainoi oieneeiaeeiaiiee AeAA aea/aeenue ca oiiae aino?iai
(aaaaeaiiy o oeoiie 5 a/ea, aeey Ae*E-AE — 1/2 DL50) ? iiaeaino?iai
(30-e?aoia aaaaeaiiy o oeoiie 1 a/ea, aeey Ae*E-AE — 1/5 i 1/20 DL50)
aenia?eiaio?a, a o aeiaaeeo Ae*E-AE oaeiae a oiiaao o?ii?/ii?
iiaaeyoeieii? ae?? (4 iin., 24,9 i 6,0 ia/i3) c o?aooaaiiyi aieeao ia
ooieoe?iiaeueiee noai ia/?iee ? e?ia. Aenia?eiaioaeueii aeaii ia?iaeaii
iaoiaeii aa?iaoeieii? noaoenoeee c aeei?enoaiiyi t-e?eoa?iy No’thaeaioa
[A.O. Eaeii, 1990].

?ACOEUeOAOE AeINEIAeAEAIUe OA ?O IAAIAI?AIIss

A ?acoeueoaoi aea/aiiy aieeao aeenia?nieo aciaa?aiee?a ia a?ineioac ?
e?euee?niee ai?no ioeea?iiaeo eeneio (AeIE, ?IE) oa ??cieo eean?a a?ee?a
yaea? (AA, IAA ? AeA), anoaiiaeaii, ui enaiia?ioeee oeueiai eeano
aeeeeeathoue ??ciioa?aeoa?i? ci?ie cacia/aieo a?io?i?/ieo i?ioean?a a
i?aaiao-i?oaiyo a caeaaeiino? a?ae niiniao oa o?eaaeino? aaaaeaiiy
niieoe ? /ano aeniiceoe?? i?ney ?o ae??.

Ia ia?oiio aoai? a oiiaao iaeii?aciai? ia?i?aeueii? ae?? AeAA
aeine?aeaeaii a?ineioac ? e?euee?niee ai?no AeIE o o?ueio i?aaiao:
ia/?ioe?, n?i’yieeao ? e?noeiaiio iiceo uo??a o aeeiai?oe?. O yae?ao
ee?oei ia/?iee ca oiiae ae?? aciaa?aiee?a Ae?, AeON-C ? Ae*E-AE
niinoa??aaeenue aeaiaoaii? ci?ie ?ioaineaiino? a?ineioaco AeIE:
aaeueioaaiiy aeeth/aiiy 3I-o?i?ae?io a AeIE (/a?ac 6 ? 24 aiaeeie i?ney
aaaaeaiiy), yea ci?ith?oueny a iiaeaeueoiio (/a?ac 48 aiae.)
noeioeyoe??th oeueiai i?ioeano (?en. 1). Ia oii? oeeo ci?i a?aecia/aii
i?aeaeuaiiy e?euee?niiai ai?noo AeIE o ia/?ioe? /a?ac 24 aiaeeie,
caiaeii (48 aiae.) — ??cea cieaeaiiy oeueiai iieacieea. Aciaa?aieee
AeI-2E ? Ae*-2N a aiaeia?/ieo oiiaao aeine?aeo ni?e/eithaaee eeoa
ae?aaeaio noeioeyoe?th aeeth/aiiy 3I-o?i?ae?io a AeIE yaea? ee?oei
ia/?iee /a?ac 48 aiaeei, a oaeiae cieaeaiiy ?? e?euee?niiai ai?noo (24
? 48 aiae. a?aeiia?aeii).

Aaeueioaaiiy a?ineioaco yaea?ii? AeIE c ianooiiith noeioeyoe??th iiaea
aooe iane?aeeii i?oeiiai eiaaeaioiiai ca’ycoaaiiy aeniei?aaeoeaieo
iaoaaie?o?a aciaa?aiee?a c ioeeaio?eueieie naeoaie AeIE ? iiaeaeueoi? ??
no?oeoo?ii? iiaeeo?eaoe??, ui ? oa?aeoa?iei aeey ?yaeo ae?aaeaieo
aaiioiene/ieo ? eaioea?iaaiieo aciniieoe, aeecueeeo ca oiii/iith
no?oeoo?ith aei aea/aieo AeAA [K.Srinivasan, 1987; J.Miller, 1988;
M.Stiborova, 1992; A.Dipple, 1995;]. I?ioa ia aeeeth/aii, ui oe?
aoaeoe iiaeooue aooe coiiaeai? aieeaii AeAA ia aca?iiae?th AeIE c
a?eeaie yaea?, a oaeiae AeIE-iie?ia?acio aeoeai?noue [O.A. Ee?eeeiaa oa
ni?aaao., 1984; W. Schmidt, 1989 et all.; B. Strauss, 1992]. O?eueee
noeioeyoe?y neioaco AeIE a oiiaao ei?ioei/anii? ae?? aeanoeaa niieoeai,
ye? iathoue neaaeo aaiioiene/i?noue aai iooeeiii?iiioi?io aeoeai?noue
[A.A. ?acoeiaa, 1989; R. Zito, 1992].

Ia?a?nia i?aeaeuaiiy ai?noo AeIE ia oii? aaeueioaaiiy ?? neioaco o
ia/?ioe? ca ae?? ?yaeo AeAA, iiaeeeai, coiiaeaii cieaeaiiyi AeIEacii?
aeoeaiino? ? ? iaei??th c ?aaoeyoi?ieo ?aaeoe?e ee?oei ia aaaaeaiiy
aaiaoe/ii aeoeaieo enaiia?ioee?a oeueiai eeano. A?aei?/aia i?ci?oa
??cea iaae?iiy e?euee?niiai ai?noo AeIE, i/aaeaeii, ? iane?aeeii
i?eai?/aiiy a?ineioaco AeIE o iiia?aaei?e ia??iae aeine?aeaeaiiy, a
oaeiae iiaea aooe iia’ycaiei c ciaioaiiyi noaa?eueiino? AeIE ?
i?aeaeuaiiyi ?? /ooeeaino? aei ioeeaacii? aoaee AeIEacith aiane?aeie
niaoeeo?/ii? iiaeeo?eaoe?? a?iiieaeoee.

Ii?yae c i?eai?/aiiyi a?ineioaco AeIE o ee?oeiao ia/iiee, AeAA (Ae?,
Ae*E-AE) a oiiaao iaeii?aciaiai aaaaeaiiy caeaoi? oaeiae ni?e/eiyoe
aaeueioaaiiy aeeth/aiiy 3I-o?i?ae?io o AeIE yaea? ee?oei n?i’yiee?a
(/a?ac 6 ? 24 aiae.). ?acii c oei, oeae aoaeo o ee?oeiao n?i’yiee?a aoa
iaio ae?aaeaiee, i?ae o ia/?ioe? (?en. 1). Cacia/ai? ci?ie o n?i’yieeao
uo??a, i/aaeaeii, coiiaeai? caeaoi?noth AeAA i?iieeaoe /a?ac caoeniee
aaiioanoeeoey?iee aa?’?? i anooiaoe o niaoeeoi/ii eiaaeaioii aca?iiaei?
c AeIE aiiaae. Inoaii? iiaea i?ecaanoe aei iiyaeaiiy aaiaoe/ii
iaiiaiioeiiieo noaoaaeo ee?oei i ?icaeoeo niaaeeiai iaoiiaeaii?
iaoieiai?. Ioaea, iaea?aeaii aeaii na?ae/aoue i?i aaiioiene/io
iaaaciaeo AeAA aeey iioiinoaa. O yae?ao eeioei einoeiaiai iiceo i?iyae
ii?ooaiiy aeeiai?ee a?ineioaco AeIE ia aeyaeai? (?en. 1).

Iaea?aeai? aeai? aeacothoue ia oa, ui iaei??th c e?eoe/ieo i?oaiae
iioeiaeaeoth/i? aei? AeAA ia ??ai? ee?oeiiiai yae?a ? AeIE, aiineioac
? ai?no yei? iioa?iiee ae?aaeaii i caeiiiii?ii ciiie. Iaeaieueo cia/i?
ii?ooaiiy a?ineioaco AeIE oa ci?ie ?? e?euee?niiai ai?noo i?ae aieeaii
AeAA aeyaeeeny a ia/?ioe?, yeie iaeaaeeoue i?iaiaeia ?ieue a
iaoaaie?/i?e aeoeaaoe?? aeoiaeieo iio?iaiiiiaciaaicieia oeyoii
iaoaaiei/ieo ia?aoai?aiue c oi?ioaaiiyi aaiaoe/ii aeoeaieo iaoaaieioia
(aiae?ieneeaiiiia, a?eeaiiiia, iioiaeieo aaiceaeeio). Iaio /ooeeaei
i?aaiii aei aaiioiene/ii? ae?? oeeo niieoe ? n?i’yieee ? ia/ooeeaei —
e?noeiaee iicie. C o?aooaaiiyi e?eoa???a, ye? oa?aeoa?ecothoue
ii?ooaiiy iai?io AeIE, aa?aieee Ae?, AeON-C ? Ae*E-AE iiaeooue aooe
a?aeianai? aei niieoe, ui iathoue neeueiee oa iii??ii ae?aaeaiee
aaiioiene/iee aoaeo a oiiaao iaeii?aciaiai aaaaeaiiy, a AeI-2E ?
Ae*-2N — aei niieoe c neaaeith aaiioiene/iith aeoeai?noth.

Iiaeaeueo? aeine?aeaeaiiy aieeao AeAA ia a?ineioac oa ai?no AeIE, ?IE ?
yaea?ieo a?ee?a i?iaiaeeeenue o?eueee ia ia/?ioe? uo??a o ??cieo
iinoaiiaeao aenia?eiaio?a. A oiiaao 7-?aciaiai ia?i?aeueiiai aaaaeaiiy,
ia i?eeeaaei aeaio ia?ie aciaa?aieeia AeI-2E i Ae*E-AE aeyaeaii:
aaeueioaaiiy a?ineioaco AeIE o yae?ao ee?oei ia/?iee /a?ac 24 aiaeeie c
iiaeaeueoei eiai a?aeiiaeaiiyi (AeI-2E); noeioeyoe?th /a?ac 48 aiaeei
(Ae*E-AE); oaiaeaioe?th aei cieaeaiiy e?euee?niiai ai?noo AeIE (6 ? 24
aiae. i?ney ae?? AeI-2E ? Ae*E-AE a?aeiia?aeii) c iiaeaeueoei (48 aiae.)
eiai i?aeaeuaiiyi o ia/?ioe?.

Aeey o?ii?/ii? ?iaaeyoe?? Ae*E-AE ? oa?aeoa?iith ae?aaeaia aeicicaeaaeia
aeoeaaoe?y aiineioaco AeIE oa c?inoaiiy ?? ai?noo o yae?ao ee?oei
ia/?iee, ui naiae/eoue i?i iineeaiiy eeioeiii? i?ieioa?aoei? i aeanoeai
aaiioiene/iei, eaioea?iaaiiei aiiiiaciaaicieai a oiiaao o?eaaei? aei? o
iaeeo aeicao [A.E.?oaai/ee, 1977; C. Rusov, 1995]. Ioaea, cacia/aii
ciiie iiaeooue aooe iciaeith ia oieueee aaiioiene/ii? aeoeaiinoi, aea e
iioaioeieii? eaioea?iaaiii? iaaacia/iinoi niieoe oeueiai eeano ca oiiae
?o o?eaaeiai aaaaeaiiy.

Ia aiaeiiio aiae caeiiiii?ieo ciii aiineioaco i aiinoo AeIE a
i?aaiao-iioaiyo, AeAA ia aeeeeeathoue nooo?aeo ci?i oeeo ia?aiao??a ?IE
a oiiaao iaeii- oa naie?aciaiai aaaaeaiiy. Caieueoaiiy e?euee?niiai
ai?noo ?IE o ia/iioe? /a?ac 6 aiaeei i?ney iaeii?aciai? ae?? AeAA (e??i
AeI-2E) ? o iaio?e i??? /a?ac 24 aiaeeie (aeey Ae*E-AE ? Ae*-2N) iiaea
aooe coiiaeaii cieaeaiiyi ia aeayeee /an ?IEacii? aeoeaiino? ? o ca’yceo
c oeei ioe?iaii, ye iaeio c eiiiainaoi?ieo ?aaeoe?e ee?oei o
a?aeiia?aeue ia aaaaeaiiy enaiia?ioee?a. Oeae aoaeo a ie?aieo aeiaaeeao
oaeiae iia’ycaii c aeoeaaoe??th a?ineioaco ?IE (24 aiae.), iiaeeeai, ca
?aooiie i?aeaeuaiiy o?aine?eioe?eii? aeoeaiino? ia?aaaaeii oeo aai?a,
ye? a?aeiia?aeaeuei? ca neioac iecueeiiieaeoey?ieo ?IE, oa/aai ca
?aooiie noeioeyoe?? ?IE-iie?ia?acii? aeoeaiino?. Oea i?eiouaiiy
a?oioo?oueny ia oiio, ui, ye a?aeiii [O.A.Nuyenoa, 1991; D. Clavson,
1992], a?eueo?noue aaeaeoeo?a aaiioiene/ieo ai?iiaciniieoe
?icoaoiao?oueny ia ae?eyieao AeIE, ye? caaaa/ai?
aenieiiiaoi?thaaeueieie iine?aeiaiinoyie (ia?aaaaeii A-Oe-iiaoi?aie),
ui aeeiiothoue ?aaoeyoi?i? ooieoe??. O ca’yceo c oeei, i?ae aieeaii AeAA
iiaea cia/ii iineethaaoeny neioac iecueeiiieaeoey?ieo ?IE, oiae? ye
neioac aenieiiieaeoey?ieo ?IE iiaea aooe i?eai?/aiei ia aeayeee /an. A
oiiaao o?ii?/ii? ?iaaeyoe?? Ae*E-AE niinoa??aaeanue aeicicaeaaeia
aeoeaaoe?y a?ineioaco ?IE o yae?ao ee?oei ia/?iee, iia’ycaia c?
noeioeyoe??th a?ineioaco AeIE. Oeae aoaeo iiaea aooe iciaeith
i?aeaeuaiiy aeoeaiino? nenoaie o?aine?eioe?? i?e o?eaae?e ae??
enaiia?ioee?a oeueiai eeano

A?aeiia?aeii aei ci?i e?euee?niiai ai?noo AeIE ? ?IE i?ae aieeaii AeAA
anoaiiaeaii aeeiai?/i?noue ni?aa?aeiioaiy ?IE/AeIE o ia/?ioe? uo??a. A
oiiaao iaeii?aciai? ae?? AeAA aeyaeaii i?aeaeuaiiy ?IE/AeIE /a?ac 6 ? 48
aiaeei. Ca oiia 7-?aciaiai aaaaeaiiy AeAA niinoa??aaeinue i?aeaeuaiiy
?IE/AeIE /a?ac 6 ? 24 aiaeeie oa eiai cieaeaiiy /a?ac 48 aiaeei. Ca
o?ii?/ii? ae?? Ae*E-AE (25,3 ia/i3) a?aecia/aii cieaeaiiy oeueiai
iieacieea.

Aea/aii AeAA oaeiae caeaoii aeeeeeaoe niaoeeo?/i? ci?ie a?ineioaco oa
ai?noo ??cieo eean?a yaea?ieo a?ee?a (?en. 2). A oiiaao iaeii?aciaiai
aaaaeaiiy an?o AeAA /a?ac 6 ? 24 aiaeeie niinoa??aaeanue aeoeaaoe?y
a?ineioaco a?noii?a o yae?ao ee?oei ia/?iee (aeey AeI-2E — o aeaeyae?
oaiaeaioe??) o ii?aeiaii? c i?aeaeuaiiyi ?o caaaeueiiai ai?noo oa ai?noo
a?aeiinii AeIE, a oaeiae cieaeaiiyi ni?aa?aeiioaiiy IAA/AA (e??i AeI-2E
? Ae*-2N). Cacia/ai? ci?ie iiaeooue iina?aaeiuei aeacoaaoe ia
i?aeaeuaiiy no?oeoo?ecaoe?? o?iiaoeiiaiai eiiieaeno. Inoaii?, iaaii,
iiaea i?ecaiaeeoe aei ci?ie nooiaiy eiaaeaioii? aca?iiae?? aaiioiene/ieo
niieoe c AeIE o neeaae? o?iiaoeiiaeo no?oeoo?. Oe? c?ooaiiy, ye?
niinoa??aaeenue ia?aeaeueii c iaeiie/aiiyi e?euee?niiai ai?noo AeIE oa
?IE, oaeiae iiaeia ioe?ieoe ye eiiiainaoi?ii-i?enoinia/? ?aaeoe??
ee?oei o a?aeiia?aeue ia iioeiaeaeoth/o ae?th AeAA, cie?aia o aeaeyae?
i?eai?/aiiy a?ineioaco AeIE. *a?ac 48 aiaeei i?ney iaeii?aciai? ae??
AeAA a?aei?/aeiny cieaeaiiy ai?noo a?noii?a (ca aeiyoeii Ae?) oa
?ioaineaiino? ?o a?ineioaco (aeey Ae*-2N ye neaaea oaiaeaioe?y) ia oii?
iaae?iiy ai?noo AeIE o ia/?ioe? (?en. 2) Iaei??th c i?e/ei oaeiai aoaeoo
? iiia?aaei? (6 ? 24 aiae.) aaeueioaaiiy a?ineioaco AeIE. Ia aeeeth/aia
oaeiae iiaeeea?noue iiaeeo?eaoe?? oeeo a?ee?a aiane?aeie eiaaeaioii?
aca?iiae?? c aciaa?aieeaie, ine?eueee, ye a?aeiii [W.Schmidt, 1989],
aaiioiene/i? ai?iiaciniieoee caeaoi? iaea?eueo ?ioaineaii aca?iiae?yoe c
AA na?aae ?ioeo eean?a yaea?ieo a?ee?a. Iciaeith inoaiiueiai iiaea
neoaeeoe iaae?iiy ai?noo AA o ia/?ioe?. A oiiaao o?ii?/ii? ae?? Ae*E-AE
(25,4 ? 5,3 ia/i3) aeyaeaii aeoeaaoe?th a?ineioaco AA, aca?iiiia’ycaio
c ?ioaineo?eaoe??th a?ineioaco AeIE ? ?IE o ia/?ioe?.

A?ineioac IAA o yae?ao ee?oei ia/?iee ca oiiae iaeii?aciai? ae?? AeAA
/a?ac 6 aiaeei ia ci?ithaaany ? o?eueee o aeiaaeeo Ae? niinoa??aaeanue
eiai aeoeaaoe?y. *a?ac 24 aiaeeie an? AeAA aeeeeeaee aaeueioaaiiy
a?ineioaco IAA (aeey Ae*-2N — o aeaeyae? neaaei? oaiaeaioe??) ia oii?
c?inoaiiy e?euee?niiai ai?noo oeeo a?ee?a o ia/?ioe? (?en. 2). Ia?oa
c?ooaiiy, iiaeeeai, iiaei aeieeiooe aiane?aeie aeieoaaiiy aai?a, ye?
a?aeiia?aeaeuei? ca neioac IAA, aeoiaey/e c anoaiiaeaiiai oaeoo
aaeueioaaiiy a?ineioaco AeIE ia oeueiio ae aoai? aeine?aeaeaiue. Aea
ine?eueee aaeueioaaiiy neioaco IAA ia o an?o aeiaaeeao a?aeaoaaeiny
ia?aeaeueii c i?eai?/aiiyi neioaco AeIE, oi oeae aoaeo oaeiae iiaea
aooe coiiaeaiei ii?ooaiiyi i?ioeano o?aineyoe??. I?aeaeuaiiy ai?noo IAA
? ni?aa?aeiioaiiy IAA/AA, iiaeeeai, aeieea? ca ?aooiie cieaeaiiy
aeoeaiino? i?ioean?a eaoaaie?cio a?aeiia?aeiiai eeano a?ee?a ?
a?aeiinii oeueiai ia? eiiiainaoi?iee oa?aeoa?. *a?ac 48 aiaeei i?ney
iaeii?aciai? ae?? AeAA neioac IAA a?aeiiaethaaany, a o aeiaaeeo AeI-2E
? AeON-C a?aei?/aii eiai neaaeo noeioeyoe?th (?en. 2). Ii?yae c
aeuaicia/aieie ci?iaie, niinoa??aaeinue iaae?iiy ai?noo IAA o ia/?ioe?
/a?ac 6 aiaeei i?ney ae?? Ae? ? AeON-C oa 48 aiaeei — Ae*E-AE ? AeI-2E,
ui iiaea aooe iciaeith iioeiaeaeoth/iai aieeao oeeo niieoe ia iai?i
IAA. A oiiaao o?ii?/ii? ?iaaeyoe?? Ae*E-AE ia aieeaa? ia a?ineioac
a?ee?a oeueiai eeano.

Aeey ae?? aea/aieo AeAA ? oa?aeoa?iei aaeueioaaiiy a?ineioaco aeiaoe?i?a
o yae?ao ee?oei ia/?iee, yea niinoa??aaeinue ia ??cieo aoaiao
aeine?aeaeaiue i?ney iaeii?aciaiai aaaaeaiiy niieoe. Oeae aoaeo
aeyaeaii ca oiia ae?? Ae? ? Ae*E-AE /a?ac 6, a AeON-C oaeiae ? /a?ac 24
aiae. c iiaeaeueoei eiai a?aeiiaeaiiyi (24 ? 48 aiae. aeey Ae? ? AeON-C
a?aeiia?aeii) aai noeioeyoe??th (24 aiae. aeey Ae*E-AE). I?ae aieeaii
Ae*-2N aaeueioaaiiy a?ineioaco AeA niinoa??aaeinue /a?ac 24 ? 48 aiaeei,
a aeey AeI-2E — eeoa 48 aiaeei c iiia?aaei?i i?aeaeuaiiyi eiai
?ioaineaiino? (6 ? 24 aiae. a?aeiia?aeii). Ia ia?oiio aoai? (6 aiae.)
aaeueioaaiiy neioaco AeA anoaiiaeaii o?eueee aeey oeo aciaa?aiee?a, ye?
o oie aea /an aaeueioaaee a?ineioac AeIE (oiaoi Ae?, AeON-C ? Ae*E-AE),
i?ci?oa — aeey ?aooe niieoe (AeI-2E ? Ae*-2N), ye? noeioethaaee neioac
AeIE /a?ac 48 aiaeei (?en. 1, 2). A aiaeia?/ieo oiiaao aeine?aeo oaeiae
aeyaeaii ??cea cieaeaiiy e?euee?niiai ai?noo AeA o ia/?ioe? /a?ac 24
aiae. i?ney ae?? AeON-C, oa i?aeaeuaiiy — /a?ac 48 aiae. i?ae aieeaii
an?o AeAA (aeey AeON-C ? Ae? — o aeaeyae? oaiaeaioe??). Inoaii?,
i/aaeaeii, coiiaeaii ii?ooaiiyi i?ioean?a eaoaaie?cio oeeo a?ee?a.
O?ii?/ia ae?y Ae*E-AE (5,3 ia/i3) i?ecaiaeeea aei aeoeaaoe?? a?ineioaco
AeA o ia/?ioe?.

AeAA a oiiaao iaeii?aciai? ae?? oaeiae iaoiiaethaaee niaoeeo?/i? ci?ie
e?eue-e?nieo a?eie-a?eeiaeo ? a?eie-ioeea?iiaeo ni?aa?aeiioaiue.
Niinoa??aaeenue ci?ie ni?aa?aeiioaiiy IAA/AA: cieaeaiiy /a?ac 6 aiaeei
(Ae?, AeON-C ? Ae*E-AE) oa i?aeaeuaiiy /a?ac 24 i?ae aieeaii an?o AeAA ?
48 aiaeei o aeiaaeeo AeON-C ? Ae*-2N; AA/AeIE: i?aeaeuaiiy /a?ac 6 ?
a?eueo ??cei — /a?ac 48 aiaeei (e??i AeI-2E); AA/?IE: iaae?iiy /a?ac 6
aiaeei (e??i AeI-2E), c?inoaiiy /a?ac 24 (aeey Ae? ? AeON-C) oa
ciaioaiiy /a?ac 48 aiaeei (o aeiaaeeo Ae*-2N ? AeI-2E). Aeey
ei?ioei/anii? ae?? AeAA oaeiae ? oa?aeoa?iei cia/ia c?inoaiiy
ni?aa?aeiioaiiy IAA/AeIE ? o a?eueo?e i??? AeA/AeIE /a?ac 48 aiaeei
i?ney ?o aaaaeaiiy.

Aeyaeai? i?ae aieeaii AeAA ii?ooaiiy a?ineioaco oa ci?ie e?euee?niiai
ai?noo ? ni?aa?aeiioaiue AeIE ? ??cieo eean?a a?ee?a yaea? (AA, IAA ?
AeA) o ia/?ioe? oa n?i’yieeao uo??a o aeeiai?oe? na?ae/aoue i?i
aaiioiene/io aeoeai?noue oeeo niieoe. Cacia/ai? e?eoa??? iiaeooue
aeei?enoiaoaaoenue aeey ioe?iee aaiioiene/ieo aeanoeainoae iiaeo niieoe
oeueiai eeano (iio?aeieo i?o?iai?iiaciaaicieo).

Ii?ooaiiy a?ineioaco AeIE oa yaea?ieo a?ee?a a cia/i?e i??? iiaeooue
aooe iia’ycai? c iooaaaiiith aeoeai?noth AeAA, yea anoaiiaeaia o ??cieo
eaoaai??yo ei?ioei/anieo oano?a (E*O). Aea/aii AeAA aeyaeee
iooaaaii?noue o oanoi Aeina, iiaeoeoth/e ia?aaaaeii o?aei-oeoo aaiii
iooaoei? ia ooaii S. typhimurium OA-98, a iaioie ii?i iooaoei? caiiie
ia?e ioeeaioeaeieo iniia ia ooaii OA-100 ye a nenoaii c iaoaaiei/iith
aeoeaaoei?th, oae i aac ia?. Aeoiaey/e c io?eiaieo aeaieo
oeeoiaaiaoe/iiai aiae?co ee?oei e?noeiaiai iiceo uo??a in vivo, AeAA a
oiiaao 6-?aciai? ia?i?aeueii? aei? (Ae*E-AE, AeON-3, Ae*-AE i Ae?) oa
o?iii/ii? ?iaaeyoe?? (Ae*E-AE) ni?e/eiythoue no?oeoo?ii iioeiaeaeaiiy
o?iiinii a niiaoe/ieo eeioeiao. Aaiaoe/ii ii?ooaiiy o noaoaaeo eeioeiao
uo?ia-naioeia aeyaeaii ia i?eeeaae? Ae*E-AE, aeine?aeaeaiiai a oiiaao
o?iii/ii? aei? ia ?iaii 25,4 i 5,3 ia/i3. Oeae aciaa?aiee coiiaethaaa
aeicicaeaaeio iiaeoeoeith AeEI o noaoaaeo eeioeiao ia iiciio noaaeiyo
nia?iaoiaaiaco, i?i ui naiae/eoue iiaeaeuaiiy caaaeueii? aia?iiiaeueii?
nia?oiinoi ia?aaaaeii ca ?aooiie iinoiiieaioaoeieieo i a iaioie ii?i
aeiiiieaioaoeieieo ao?ao. ?aooo AeAA ii aiaeiai? c Ae*E-AE i ?aiioa
aea/aiei AeI-2E [N.?.Oeiei, 1992], yei iathoue iooaaaiio aeoeaiinoue o
oanoi AeEI, oaeiae iiaeia aiaeianoe aei iioaioeieii iaaacia/ieo ?a/iaei
ii iioeiaeaeoth/ie aei? ia aaiaoe/iee aia?ao noaoaaeo eeioei.
Aciaa?aieee eeaneo?eiaai? a caeaaeiinoi aiae nooiaith iooaaaiiiai aoaeoo
o ??cieo E*O [E.I.Oiiooaei ? niiaaao.,1977; A.B.Naiioeueeee,1979;
I.I.Ai/eia, 1989].

AeAA aeyaeythoue niaoeeoi/io aeith ia ?ai?iaeoeoeaio nenoaio
uo??a-naioeia. Oeae aoaeo i?iyaey?oueny o aeaeyae? aaeueioaaiiy
a?ineioaco AeIE ? iooaoe?e o noaoaaeo ee?oeiao, ye iieacaii aeua, a
oaeiae aeeno?ioi/ieo i iae?iaiioe/ieo ciii nii’yieo eaiaeueoeia, ui
caeii/oaaeenue cionoioaiiyi cia/ii? ?o /anoeie. Aeyaeaii oaeiae ciiie
ooieoeiiiaeueieo i ii?oiiao?e/ieo iieacieeia, ui naiae/aoue i?i
ii?ooaiiy i?ioeano nia?iaoiaaiaco.

Iniaeeainoth oieneeiaeeiaiiee AeAA ? ii?ooaiy ooieoe?iiaeueiiai noaio
ia/iiee. Oa?aeoa?iei i?iyaii caaaeueiioiene/ii? aei? aciaa?aiee?a oaeiae
? a?aaeaiiy a?eo?ioeeo?a o aeaeyaei iao- i noeueoaaiiaeiaiiaii? c
ianooiiith aeano?oeoei?th aaiiaeia?io oa ooai?aiiyi oieaoeue Aaeioey i,
ye ianeiaeie, ?icaeoeo aiaii?.

Niaoeeo?/i? ci?ie a?ineioaco ? ai?noo AeIE ? yaea?ieo a?ee?a
(AA, IAA), ii?yae c e?eoa??yie iooaaaiiino? oa aiiaaeio?iiiino?, aoee
aeei?enoaii c iaoith iaa?oiooaaiiy AAeE aea/aieo AeAA o iiaio?i ?iai/i?
ciie.

Aeey aciaa?aieea Ae*E-AE, ii?iiaaiiai ca iiaiith i?ia?aiith
oieneeieiai/ieo aeineiaeaeaiue, a oiiaao o?iii/ii? iiaaeyoei? ii??a
oe?aeeeai? ae?? ca e?eoa?iyie caaaeueii? oiene/iinoi (aaiaoi- i
iae?ioiene/iee aoaeo) — Limch ia?aaeuo? 6 ia/i3, i?ioa ii??a
a?aeaeaeaieo aoaeo?a ca e?eoa??yie aaiioiene/iino? ? aiiaaeio?iiiino? —
Limch sp ciaoiaeeoueny cia/ii ieae/a 5 ia/i3. A?aoiaoth/e aieueo
ae?aaeaii aiiaaeio?iiii i iniaeeai aaiioiene/ii aeanoeainoi oeueiai
aa?aieea ii?iaiyii c AeI-2E — ?iaeiia/aeueieeii ?yaeo AeAA, ii?iiaaiiai
c o?aooaaiiyi aiaeaeaeaieo aoaeoia ia ?iaii 0,5 ia/i3 [I.A. Aauoe,
1989], ye AAeE aeey Ae*E-AE ?aeiiaiaeiaaia i caoaa?aeaeaia aaee/eia 0,3
ia/i3 (aa?icieue, II eean iaaacia/iinoi).

Aecia/aia ia i?eeeaaei Ae*E-AE aieueo aeniea iioi?iaoeaia cia/ouinoue
e?eoa?i?a iioeiaeaeoth/i? aei? ia aaiaoe/iee aia?ao i ?ai?iaeoeoeaio
nenoaio o ii?iaiyiii c e?eoa?iyie caaaeueii? oiene/iinoi iiaeoaa?aeaeaia
oaeiae ia i?eeeaaei ?aooe AeAA, ii?iiaaieo c aeei?enoaiiyi i?eeiio
aiaeiai? o ?yaeao niieoe, aeecueeeo ca oiii/iith no?oeoo?ith oa
aiieiai/iith aei?th. Nia?oo aiai?ii/ii ?aaeaiaioe aeey AeON-3, Ae*-AE,
Ae*-2N i Ae? aoee iaa?oioiaaii oieueee c o?aooaaiiyi caaaeueiioiene/ieo
e?eoa?i?a (a iniiaiiio aaiioiene/iiai aoaeoo). Iaeiae iaea?aeaii iaie
aeaii, yei naiae/aoue i?i ?o aaiioiene/io aeoeaiinoue, iaa?oioiaothoue
iaiaoiaeiinoue ei?eaoaaiiy caoaa?aeaeaieo aeey ieo aaee/ei AAeE o aie
cieaeaiiy. Ineieueee aciaa?aieee AeON-3 i Ae? aeecueei ii nooiaith
ae?aaeaiinoi aaiioiene/iiai ? aiiaaeio?iiiiai aoaeoo aei Ae*E-AE, aeey
ieo ?aeiiaiaeiaaia oaea ae aaee/eia AAeE, ui i aeey Ae*E-AE, oiaoi 0,3
ia/i3 (II eean iaaacia/iinoi). Aeey Ae*-AE i Ae*-2N c o?aooaaiiyi
nooiaiy ae?aaeaiinoi niaoeeoi/ieo aiaeaeaeaieo aoaeoia (a iniiaiiio
aaiioiene/iiai) AAeE ?aeiiaiaeiaaii ia ?iaii 0,5 ia/i3 ii aiaeiai? c
AeI-2E.

A?aoiaoth/e anoaiiaeaio iaie nooiiiue ae?aaeaiinoi aaiioiene/iiai i
aiiaaeio?iiiiai aoaeo?a a ?yaeo aea/aieo AeAA, na?aae e?eoa?i?a
niaoeeoi/ii? aei? i?ii?eoaoieie aeciaii e?eoa?i? aaiioiene/iino?: ci?ie
aiineioaco AeIE, AA ? IAA o yae?ao eeioei ia/iiee oa n?i’yiee?a,
iiaeoeoeiy ?icieo oeiia OA a eeioeiao einoeiaiai iiceo, iiaeoeoeiy AeEI.
Ae?oaa iinoea ii iioi?iaoeaiinoi caeiathoue e?eoa?i? aiiaaeio?iiii?
aei? (ii?oino?oeoo?ii ciiie oaenoeeoey?ii? oeaieie oa eiiieaen
ii?oiiao?e/ieo iieacieeia). Ia oe?e iniia? aenia?eiaioaeueii
iaa?oioiaaii oaeineiiaeaiee iaoiaee/iee iiaeoiae, yeee iiaea aooe
aeei?enoaiee aeey aeyaeaiiy aiaeaeaeaieo aoaeoia (iioeiaeaeoth/i? aei?
ia aaiaoe/iee aia?ao ? ii?ooaiue ?ai?iaeoeoeaii? nenoaie) i aiai?ii/iiai
?aaeaiaiooaaiiy AeAA.

AENIIAEE

1. ??ciini?yiiaai? ci?ie aeeiai?ee a?ineioaco eiiiiiaio?a o?iiaoeio oa
ii?ooaiiy eiai ?aaoeyoe?? ca oiia ae?? aaiaoe/ii aeoeaieo enaiia?ioee?a
iaoiiaeththoue ii?ooaiiy iaoaaie?/ieo i?ioean?a o ee?oeiiiio yae?? oa,
c?aooith, i?ioean?a ?aaoeyoe?? ee?oeiiiai aiiainoaco a i?aaiao ?
oeaieiao.

2. AeIE-neioacoth/a aeoeai?noue yaea?iiai aia?aoo ee?oei ia/?iee oa
n?i’yiee?a i?ae aieeaii ?yaeo iio?aeieo 4-i?o?i-4’-ai?iiaciaaicieo
(aeenia?nieo aciaa?aiee?a) i?ney ei?ioei/anii? ?o ae?? i?eai?/o?oueny
i?iaeiaae aeiae oa noeioeth?oueny ia 48 aiaeeio; ca oiia o?ii?/ii? ae??
a?aeaoaa?oueny aeicicaeaaeia aeoeaaoe?y a?ineioaco AeIE. Iaea?eueo?
ci?ie a?ineioaco AeIE niinoa??aathoueny o ia/?ioe?, iaio ae?aaeai? o
n?i’yieeao oa ia aeyaeythoueny o e?noeiaiio iiceo.

3. Aeeiai?ea a?ineioaco oa e?euee?noue ?IE o yae?ao ee?oei ia/?iee ca
ei?ioei/anii? ae?? i?o?iai?iiaciaaicie?a ia cacia? nooo?aeo ci?i, i?ioa
a oiiaao ?o o?ii?/ii? ae?? a?ineioac ?IE ei?aeth? c aeeiai?eith
a?ineioaco AeIE ca oeeo aea oiia.

4. A?ineioac a?noiiiaeo a?ee?a o yae?ao ee?oei ia/?iee i?ae
ei?ioei/aniei aieeaii i?o?iai?iiaciaaicie?a noeioeth?oueny /a?ac 6 ? 24
aiaeeie i?ney ?o aaaaeaiiy oa i?eai?/o?oueny /a?ac 48 aiaeei, oiae? ye
a?ineioac iaa?noiiiaeo a?ee?a ca oeeo aea oiia aaeueio?oueny /a?ac 24
aiaeeie c iiaeaeueoei eiai a?aeiiaeaiiyi (aeey ie?aieo niieoe —
noeioeyoe??th). O?ii?/ia ae?y aea/aieo i?o?iai?iiaciniieoe ni?e/eiy?
aeoeaaoe?th a?ineioaco a?noiiiaeo a?ee?a i?e a?aenooiino? ci?i neioaco
IAA. Cacia/ai? c?ooaiiy na?ae/aoue i?i ci?ie no?oeoo?e oa
ooieoe?iiaeueii? aeoeaiino? o?iiaoeiiaiai eiiieaeno i?ae aieeaii
i?o?iai?iiaciaaicie?a.

5. Aeeiai?ea a?ineioaco aeiaoe?iiaeo a?ee?a o yae?ao ee?oei ia/?iee ca
oiiae ei?ioei/anii? ae?? ? niaoeeo?/iith aeey eiaeiiai aea/aiiai
iio?aeiiai 4-i?o?i-4’-ai?iiaciaaicieo. Aeey Ae? ? Ae*E-AE a?ineioac AeA
aaeueio?oueny /a?ac 6, a AeON-C oaeiae ? /a?ac 24 aiaeeie c iiaeaeueoei
(48 aiae.) eiai a?aeiiaeaiiyi aai noeioeyoe??th; aeey Ae*-2N — /a?ac 24
? 48 aiaeei, a aeey AeI-2E — o?eueee 48 aiaeei c iiia?aaei?i
i?aeaeuaiiyi eiai ?ioaineaiino?. I?ioa an? i?o?iai?iiaciniieoee /a?ac
48 aiaeei iaoiiaeththoue c?inoaiiy e?eueeino? AeA o ia/?ioe?.

6. Ci?ie e?euee?nieo a?eie-a?eeiaeo oa a?eie-ioeea?iiaeo ni?aa?aeiioaiue
o yae?ao ee?oei ia/?iee ca ei?ioei/anii? ae?? i?o?iai?iiaciaaicie?a
oa?aeoa?ecothoueny cieaeaiiyi (/a?ac 6 aiae.) oa i?aeaeuaiiyi (24 aiae.)
IAA/AA, i?aeaeuaiiyi (48 aiae.) AA/AeIE, IAA/AeIE oa AeA/AeIE.

7. Ei?ioei/ania ae?y i?o?iai?iiaciaaicie?a i?ecaiaeeoue aei
??ciini?yiiaaieo ci?i a?ineioaco ioeea?iiaeo eeneio ? a?ee?a c
ii?ooaiiyi ei?aeyoe?? aeeiai?ee oeeo i?ioean?a. Ia a?aei?io a?ae ia?,
o?ii?/iee aieea oeeo niieoe iaoiiaeth? ni?aiaaeath/? ci?ie (aeoeaaoe?th)
aeeiai?ee a?ineioaco. Oe? i?ioeane iia’ycai? a?aeiia?aeii c
?i?oe?aoe??th oa ?icaeoeii aeyaeaieo a?aeaeaeaieo aoaeo?a (iooaaaiiiai
oa aiiaaeio?iiiiai), coiiaeaieo ae??th i?o?iai?iiaciniieoe.

8. Ia i?aenoaa? io?eiaieo ?acoeueoao?a cai?iiiiiaaii eiiieaen iaea?eueo
iioi?iaoeaieo e?eoa???a ioe?iee iioeiaeaeoth/i? ae??
i?o?iai?iiaciaaicie?a ia i?aai?ci oa aiai?ii/iiai ?aaeaiaiooaaiiy niieoe
oeueiai eeano. Oaeeie e?eoa??yie ? ci?ie a?ineioaco AeIE, AA ? IAA o
yae?ao ee?oei ia/?iee oa n?i’yiee?a; ?iaeoeoe?y o?iiiniiieo aaa??aoe?e
o ee?oeiao e?noeiaiai iiceo; i?aeaeuaiiy /anoioe AeEI; e?eoa???
aiiaaeio?iiii? ae??. C ?o aeei?enoaiiyi ?aeiiaiaeiaaii cieaeaiiy AAeE o
iia?o?? ?iai/i? ciie aeey aciaa?aiee?a, ye? ii?iiaaii ?aiio ia aieueo
aenieiio ?iaii eeoa c o?aooaaiiyi e?eoa?i?a caaaeueii? oiene/iinoi.

IOAEIEAOeI? INIIAIEO IIEIAEAIUe AeENA?OAOeIEII? ?IAIOE

1. Oieneeieiae/aneay ioeaiea acie?aneoaey aeenia?niiai E?aniiai 2N
iieeyoe?iiai / A.E. Caacaeae, E.A. Iaeaaeia, E.I. Eiaai, A.A.
Naaioeoeeee // Aeaeaia o?oaea e i?io. caaieaaaiey.- 1989.- N 12.- C. 56.

2. Caacaeae A.E., Iaeaaeia E.A.,Eaethaeiue A.E. E?aneoaeue i?aaie/aneee
aeenia?niue iieeyoe?iue E?aniue AE // Oieneeieiae/. aanoiee.- 1994.- N
5.- C.41-42.

3. Auyaeaiea aaiioiene/aneie e iooaaaiiie aeoeaiinoe aeenia?niuo
acie?aneoaeae n oeaeueth eo aeaeaie/aneiai ii?ie?iaaiey / E.A.Iaeaaeia,
Ae.I.Aeaaaeeen, I.A.Aauoe,A.E.Eaethaeiue // Iaaeeoeeia o?oaea e i?ii.
yeieiaey.-1995.-N5.-C.12-15

4. Iaeaaeia E.A. Aeeyiea aeenia?niuo acie?aneoaeae ia aeineioac
ioeeaeiiauo eeneio // I?iaeaiu e?eiaeieiaee.- 1997.- N 3.- N. 68-69.

5. Iaeaaeia E.A. Iniaaiiinoe aeineioaca aenoiiiauo e iaaenoiiiauo aaeeia
i?e aicaeaenoaee aeenia?niuo acie?aneoaeae // I?iaeaiu e?eiaeieiaee.-
1997.- N 4.- N. 65-66.

6. Iaeaaeia E.A. N?aaieoaeueiay oieneeieiae/aneay ioeaiea ?yaea
aeenia?niuo acie?aneoaeae n oeaeueth eo aeaeaie/aneiai ?aaeaiaioe?iaaiey
// Aanoiee i?iaeai aeieiaee e iaaeeoeeiu.- 1997.- N 26.- N. 127-140.

7. Palagina I.A. Studies on molecular mechanisms of genotoxic effect of
disperse azo dyes — aminoazobenzene derivatives // School of fundamental
medicine journal.- 1997.- Vol. 3, No 2.- P. 31-36.

8. Iaeaaeia E.A. E?aneoaeue i?aaie/aneee aeenia?niue E?anii-ei?e/iaaue
AE // Oieneeieiae/aneee aanoiee.- 1998.- N 1.- C. 40.

9. Iaeaaeia E.A. Aeeyiea aeenia?niuo acie?aneoaeae ia ninoiyiea
aaiaoe/aneiai aiia?aoa / Iaaeeoeeia naaiaeiy e caao?a: Na. iao/. ?aaio
iieiaeuo o/aiuo e niaoeeaeenoia. — Oa?ueeia: OAIO, 1996.- C. 241-243.

10. Iaeaaeia E.A. Aeaeaie/aneia ?aaeaiaioe?iaaiea aeenia?niiai
iieeyoe?iiai e?aneoaey E?anii-ei?e/iaaiai AE a aicaeooa ?aai/ae ciiu n
o/aoii ioaeaeaiiuo yooaeoia // Aeieiae/aneia aeaenoaea oaeoi?ia
ie?oaeathuae n?aaeu: Ca. iao/. o?.- Oa?ueeia: OAIE, Oa?Ai?NYN, 1996.-
C. 230-234.

11. Caacaeae A.E., Iaeaaeia E.A. Ii?oi-ooieoeeiiaeueiua e aaiaoe/aneea
ia?ooaiey ?ai?iaeoeoeaiie ooieoeee ieaeiieoathueo i?e aicaeaenoaee
aeenia?niuo acie?aneoaeae // Aanieiaeea. Aniiiiaaoaeueiua
?ai?iaeoeoeaiua oaoiieiaee: Na. iao/. o?. neiiiceoia n iaaeaeoia?iaeiui
o/anoeai (Eeaa, 15-16 iay 1997).- E.: Ei-o ?ai?iaeoeoeaiie iaaeeoeeiu
OAIII, 1997.- C. 172-174.

12. Aaiaoe/ia iaaaciaea aeenia?nieo aciaa?aieeia ye eiiiooth/ee e?eoa?ie
i?e iaa?oiooaaiii aiai?ii/ieo ?aaeaiaioia ae?iaie/iai na?aaeiaeua / A.I.
Caacaeae, A.A. Ooaeieie, I.A. Iaeaaiia, A.E. Eaethaeiee // Iaoa?iaee II
c’?caeo iaaee/ieo aaiaoeeia Oe?a?ie (Eueaia, 18-20 aeiaoiy 1995).-
Eueaia.- 1995.- C. 70.

13. Iooaaaiiay e iioaioeeaeueiay eaioea?iaaiiay iianiinoue aeenia?niuo
acie?aneoaeae aeey iieeyoe?iuo aieieii / A.E. Caacaeae, E.A. Iaeaaeia,
Ae.I. Aeaaaeeen, A.E. Eaethaeiue // Aeooaeueiua aii?inu
i?ioeeaeoe/aneie iaaeeoeeiu: Iaoeu iao/ii-i?aeoe/aneie eiio.- Oa?ueeia:
OAIO, Oa?Ai?NYN, 1996.- C. 25-26.

AIIOAOeIss

Iaeaaiia I.A. Aieea aeenia?nieo aciaa?aieeia ia aiineioac ioeea?iiaeo
eeneio i aieeia c o?aooaaiiyi aiaeaeaeaieo aoaeoia.- ?oeiien.

Aeena?oaoeiy ia caeiaoooy iaoeiaiai nooiaiy eaiaeeaeaoa aiieiai/ieo iaoe
ca nia-oeiaeueiinoth 03.00.04 — aiioiiiy.- Oa?eianueeee aea?aeaaiee
oiiaa?neoao, Oa?eia, 1999.

Aeena?oaoeith i?enay/aii aea/aiith aiineioaco AeIE, ?IE, a?noiiiaeo,
iaa?noiiiaeo ? aeiaoe?iiaeo a?ee?a o yae?ao ee?oei ia/?iee, n?i’yiee?a
oa e?noeiaiai iiceo uo??a i?ae aieeaii aeenia?nieo aciaa?aiee?a (AeAA) c
o?aooaaiiyi a?aeaeaeaieo aoaeo?a.

Anoaiiaeaii, ui ei?ioei/ania ae?y AeAA ni?e/eiy? ??ciini?yiiaai? ci?ie
a?ineioaco ioeea?iiaeo eeneio ? a?ee?a c ii?ooaiiyi ei?aeyoe?? oeeo
i?ioean?a. AeIE-neioacoth/a aeoeai?noue yaea?iiai aia?aoo i?ney ae??
AeAA i?eai?/o?oueny c iiaeaeueoith noeioeyoe??th ca a?aenooi?noth ci?i
a?ineioaco ?IE. Ca oeeo oiia a?ineioac AA ci?ith?oueny i?ioeeaaeii aei
aeeiai?ee a?ineioaco AeIE, aaeueio?oueny a?ineioac IAA ? AeA. O?ii?/ia
ae?y AeAA i?ecaiaeeoue aei aeoeaaoe?? a?ineioaco AeIE, ?IE ? AA.
Iaea?eueo? ci?ie a?ineioaco niinoa??aathoueny o ia/?ioe?, iaio ae?aaeai?
o n?i’yieeao oa ia aeieeathoue o e?noeiaiio iiceo. An? oe? ci?ie
iia’ycai? c iooaaaiiei oa aiiaaeio?iiiei aoaeoaie AeAA. Aecia/ai?
e?eoa?i? aaiioiene/ii? i aiiaaeio?iiii? aei? aeeo?enoaii i?e
iaa?oiooaaiii AAeE aeey AeAA.

Eeth/iai neiaa: aiineioac, AeIE, ?IE, ainoiiiai, iaa?noiiia? oa
aeiaoe?iia? aieee, aeenia?nii aciaa?aieee, aaiioiene/iee i
aiiaaeio?iiiee aoaeoe.

AIIIOAOeEss

Iaeaaeia E.A. Aeeyiea aeenia?niuo acie?aneoaeae ia aeineioac ioeeaeiiauo
eeneio e aaeeia n o/aoii ioaeaeaiiuo yoaeoia.- ?oeiienue.

Aeenna?oaoeey ia nieneaiea o/aiie noaiaie eaiaeeaeaoa aeieiae/aneeo iaoe
ii niaoeeaeueiinoe 03.00.04 — aeioeiey.- Oa?ueeianeee ainoaea?noaaiiue
oieaa?neoao, Oa?ueeia, 1999.

Aeenna?oaoeey iinayuaia eco/aieth aeineioaca AeIE, ?IE, aenoiiiauo,
iaaenoiiiauo e aeiaoeeiiauo aaeeia a yae?ao eeaoie ia/aie, naiaiieeia e
einoiiai iicaa e?un i?e aicaeaenoaee aeenia?niuo acie?aneoaeae (AeAE) n
o/aoii ioaeaeaiiuo yooaeoia.

Onoaiiaeaii, /oi e?aoein?i/iia aicaeaenoaea AeAE aucuaaao
?aciiiai?aaeaiiua eciaiaiey aeineioaca ioeeaeiiauo eeneio e aaeeia n
ia?ooaieai ei?aeyoeee yoeo i?ioeannia. AeIE-neioace?othuay aeoeaiinoue
yaea?iiai aiia?aoa iinea aicaeaenoaey AeAE oaiaoaaony n iineaaeothuae
noeioeyoeeae i?e ionoonoaee eciaiaiee aeineioaca ?IE. A yoeo oneiaeyo
aeineioac AA eciaiyaony i?ioeaiiieiaeii e aeeiaieea aeineioaca AeIE,
eiaeae?oaony aeineioac IAA e AeA. O?iie/aneia aicaeaenoaea AeAE
i?eaiaeeo e aeoeaaoeee aeineioaca AeIE, ?IE e AA. Iaeaieueoea eciaiaiey
aeineioaca iaaethaeathony a ia/aie, iaiaa au?aaeaiiua a naiaiieeao e ia
iaia?oaeeaathony a einoiii iicaa. Ana yoe eciaiaiey naycaiu n
iooaaaiiui e aiiaaeio?iiiui yooaeoaie AeAE. Auyaeaiiua e?eoa?ee
aaiioiene/aneiai e aiiaaeio?iiiiai aeaenoaey eniieueciaaiu i?e
iainiiaaiee IAeE aeey AeAE.

Eeth/aaua neiaa: aeineioac, AeIE, ?IE, aenoiiiaua, iaaenoiiiaua e
aeiaoeeiiaua aaeee, aeenia?niua acie?aneoaee, aaiioiene/aneee e
aiiaaeio?iiiue yooaeou.

SUMMARY

Palagina I.A. Influence of the disperse azo dyes on the nucleic acids
and proteins biosynthesis, with consideration of their long-term
effects.- Manuscript.

Thesis for Ph.D. degree by speciality 03.00.04 — Biochemistry.- Kharkov
State University, Kharkov, 1999.

The thesis is devoted to the research over the DNA, RNA, histone,
non-histone and globuline proteins (HP, NHP, GlP) biosynthesis in the
nuclei of the liver, testicles and bone marrow cells of the rats under
the disperse azo dyes (DADs) influence with special emphasis on the
long-term effects.

Within experiments animals were exposed to the number of the disperse
azo dyes: Red Brown G, Red 2S, Dark Blue Z, Orange 2K, Ruby, and Red G.
These compounds by their chemical structure refer to the
4-nitro-4’-aminoazobenzene derivatives. They vary by the nature of the
benzene rings and amino-group substitutes.

Peculiarities of the nucleic acids and different classes of the nucleic
proteins biosynthesis under the DADs’ impact were studied in 3 variants
of the in vivo experiment: within, first, the short-term tests, i.e.
one-fold per os DADs injection dosed by 5 g/kg (Red Brown G, 1,6 g/kg =
1/2 DL50), second, 7-fold per os injection of the Orange 2K (dosed by 1
g/kg) and Red Brown G (0,32 g/kg = 1/10 DL50), and third, chronic
inhalation of the Red Brown G (4 months; dosed by 25,4 and 5,3 mg/m3).
Indices were defined dynamically, in 6, 24 and 48 hours after the last
azo-dyes injection.

The research showed that azo dyes’ influence causes the diverse changes
of the synthetic processes in the target organs. Their nature proved to
depend on the mode and longitude of the DADs injection as well as on the
time of the ex-post exposition.

Short-term influence of the azo dyes compounds stipulated inhibition of
the DNA-synthesizing activity of the nuclear apparatus within 24 hours
after their injection with its future (after 48 hours) stimulation.
Chronic injection of the DADs caused the dose-dependent activation of
the DNA biosynthesis. The most essential shiftings in the DNA
biosynthesis dynamics were fixed in the liver, the lesser in the
testicles and were not found in the bone marrow. This fact points out
the organic selectivity of the genotoxic impact of the studied azo
compounds.

Dynamics of the RNA biosynthesis in nuclei of the liver cells under the
short-term DAD influence proved not to be subject to a serious change.
Registered increase of the RNA content in the liver in 6 and (to a
lesser degree) 24 hours after the one-fold DAD impact is explained by
decrease of RNAoze activity and attributed as a compensatory reaction of
cells towards the xenobiotics injection. However, under chronic azo
dyes exposition the dose-dependent activation of the RNA biosynthesis
was observed; this correlated with the DNA biosynthesis dynamics under
the same conditions.

The DADs influence proved to modify the biosynthesis, content and ratios
of the various classes of the nucleic proteins. In the short-term
experiment, within 24 hours after the DAD injection the intensity of
the biosynthesis and content of the HP in the nuclei of the liver cells
increased, and after 48 hours, decreased. Such shiftings contrast with
the DNA biosynthesis dynamics under the same conditions. The NHP
biosynthesis in the similar experiment was inhibited 24 hours after the
azo dyes injection, with its further (in 48 hours) restoration, and in
case of some DADs, with its stimulation. The long-time DADs impact
proved to cause the HP biosynthesis activation; this process was
interconnected to the increase in the DNA and RNA synthesis in the liver
over the absence in the NHP biosynthesis changes. All mentioned
shiftings witness that the azo dyes are apt to modify structure and
functional activity of the chromatine complex.

The GlP biosynthesis dynamics in the nuclei of the liver cells under the
short-term exposition proved to be specific for each studied azo dye.
Under the Red Brown G and Ruby influence the process is depressed in 6,
and the Dark Blue Z in 6 and 24 hours with its future (48 hours)
restoration or stimulation; under the Red 2S impact, it is inhibited in
24 and 48 hours, and under the Orange 2K it takes place in 48 hours.
However, all studied compounds after 48 hours stipulate for the increase
of the GlP content in the liver.

The short-term influence of the azo dyes proved to specifically change
the protein-protein and protein-nucleic ratios. This was expressed in
the NHP/HP decrease (in 6 hours) and rise (24 hours), as well as in the
HP/DNA, NHP/DNA and GlP/DNA increase (in 48 hours after the DADs
impact).

The exposed changes in the nucleic acids and proteins biosynthesis under
the short- and chronic DADs influence can be connected to resp.
initiation and advancement of the long-term effects (mutagenic and
gonadotropic) of these xenobiotics.

The modification of the DNA, HP and NHP biosynthesis dynamics, together
with the indices of the mutagenic and gonadotropic activity have been
used as the priority criteria for proving of the researched DADs’ LPC in
the working area air, and may be recommended for hygienic
standardization of all other compounds of the DAD class.

Key words: biosynthesis, DNA, RNA, histone, non histone and globuline
proteins, disperse azo dyes, genotoxic and gonadotropic effects.

?en. 1. Aeeiaiiea aeeth/aiiy 3I-oiiiaeiio o AeIE yaea? eeioei ia/iiee
(A), einoeiaiai iiceo (A) oa nii’yieeia (A) aieeo uo?ia a oiiaao
iaeii?aciai? ia?i?aeueii? aei? AeAA

?en. 2. Iniaeeainoi aiineioaco ainoiiiaeo (A), iaainoiiiaeo (A) oa

aeiaoeiiiaeo (A) aieeia yaea? eeioei ia/iiee aieeo uo?ia a oiiaao

iaeii?aciai? ia?i?aeueii? aei? AeAA

Iiaeienaii aei ae?oeo 29.01.99 ?. Oi?iao 60o84 1/16

Oi.-ae?oe.a?e. 1,0 Cai. ? 415
Oe?aae 100 i?ei.

____________________________________________________________________

Iaae?oeiaaii ia ?ecia?aoi *I OeAIAe “?aeaea?”

i. Oa?eia, aoe. A?oaia, 4

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