anti-rad vaccine. russia. kazan. 1990-1994 yy

8/12/2019 Anti-Rad Vaccine. Russia. Kazan. 1990-1994 yy.

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Anti-radiation vaccine and specific substances for diagnosis

and therapy of radiation injury.

Slava Maliev, Dmitri Popov.

Abstract

Multifactor fundamental research under experimental and industrial conditions on farm

and laboratory animals (parabionts, gnotobionts, mice, rats, rabbits, dogs, sheep, pigs,

cattle, and horses), and also on humans (blood serum of Chernobyl NPP clean-upworkers) conducted between !"# and #$$# ha%e enabled us to establish the existence of

two pre%iously unknown phenomena&

the phenomenon of re%ersible redistribution of cytobiochemical parameters in the

blood-interstices-lymph-blood system of irradiated animals, which supportscompensatory maintenance of homeostasis'

the phenomenon of specific immunochemical reactions to the radiobiological effect,

in%ol%ing the formation of high molecular mass glycoprotein (molecular mass-#$$-#$ k*a) + radiation antigens in the lymphoid system with epitopes specific to each

form of radiation sickness , #, , , after animals ha%e been irradiated in doses

inducing the de%elopment of the cerebral (), toxic (#), gastrointestinal () andtypical () forms of acute radiation sickness, ./, , 'a0'

1hese two phenomena allowed us to de%elop a methodology for producing specific meansto pre%ent, diagnose, and treat radiation sickness (know-how) + an antiradiation %accine,

a serum and a set of diagnostics for conducting 23456 analyses'

1


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LS! "# A$$%&'A!"(S

Chernobyl clean-up workers

MM Molecular mass

Deoxyribonucleic acid D!

" "-lymphocy#e$ $- lymphocy#e

% &n#ermedia#e 'orms o' lymphoid cells

()* Cyclic adenosine monophospha#e c!M+, Circula#in. lymphocy#e /olume C0

,2 !cu#e radia#ion sickness !34

56 4peci'ic radia#ion de#erminan# 43D56 1 43D 'or cerebral !34 syndrome 43D 1

56 7 43D 'or #oxic !34 syndrome 43D 7

56 8 43D 'or .as#roin#es#inal !34 syndrome 43D 8

56 9:1 43D 'or mild #ypical !34 43D 9:156 9:7 43D 'or modera#e #ypical !34 43D 9:7

56 9:8 43D 'or se/ere #ypical !34 43D 9:8

56 9:9 43D 'or ex#remely se/ere #ypical !34 43D 9:95 coe''icien# o' speci'ici#y C4

;*


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pre/en#ion and #rea#men# o' acu#e and chronic radia#ion inuries in use #oday and were

nonspeci'ic wi#h respec# #o #he pa#ho.en-'ormin. a.en#

Nowe/erE polyclonal experimen#al s#udies o' 'arm and labora#ory animals ha/e

unambi.uously shown #ha# #he immunochemical processes #ha# occur in #he lymphoid

sys#em are de'ini#i/e wi#h respec# #o pa#ho.enesis o' #he radiobiolo.ical e''ec# and arespeci'ic #o le/el o' radia#ion o/er a wide spec#rum o' /alues HJE 81E 81aL

Compara#i/e lo.ical analysis o' #he ex#ensi/e base o' da#a #ha# had been ob#ained

by #hen by well-known radiobiolo.ical schoolsE .roups o' scien#is#s in rela#ed scien#i'ic

areas in #he Oni#ed 4#a#esE P3QE Prance and Rapan ser/ed as #he #heore#ically-basedprelude #o #hese s#udies Se will consider here #he mos# si.ni'ican# 'undamen#al

radiobiolo.ical research s#udies &n par#icularE !M Tu=in e# al H7UL isola#ed re.ak#enon

'rom plan# #issue "his subs#ance has a radioimuni=in. e''ec# on cell .enomesE

accompanied by depression o' D! syn#hesisE decreased cell di/ision and #issue .row#hE'orma#ion o' pykno#ic nucleiE chromosome 'ra.men#a#ionE and 'orma#ion o' mu#an#s !#

#he same #imeE a'#er adminis#ra#ion o' re.ak#enon and o#her radio#oxins isola#ed 'rom

irradia#ed #issuesE animals 'ailed #o display #he en#ire VbouWue#X o' radia#ion reac#ionsYsymp#oms o' acu#e radia#ion sickness o' /arious 'orms and se/eri#y could no# be

modeled in experimen#al animalsZ "he broad spec#rum o' ordinary chemical compounds

#ha# can ha/e analo.ous radiomime#ic e''ec#s #o #hose o' re.ak#enon demons#ra#es #helack o' speci'ici#y in induc#ion o' #hese e''ec#s by #he main classes o' radio#oxins

hydroperoxidesE peroxidesE polyphenolsE semiWuinines and WuininesE ke#oaldehydesE

bio.enic aminesE pro#eins and polypep#ides "hese compounds are always presen# in an

un#rea#ed animal and play a role in #he biochemical processes o' ca#abolism andanabolism #ha# main#ain homeos#asis 3adia#ion exposure induces a process in which #he

le/els o' one or ano#her class o' #hese compounds increases

"he s#udies o' ! Topylo/a e# al H78L demons#ra#e #he cri#ical impor#ance o'elimina#in. Wuinoid radio#oxins 'rom #he body in #rea#men# by hemosorp#ion o' animalsa'#er le#hal doses o' .amma irradia#ion

Q ladimiro/ e# al H[L de#ec#ed a 'rac#ion o' low molecular wei.h# D! in

#he blood plasma o' an animal exposed #o ioni=in. radia#ion "here are #wo poin#s o'

/iew on #he ori.in and role o' #his D! %ne o' #hem links i#s ori.in wi#h #he pos#-radia#ion 'ra.men#a#ion o' chroma#in 'rom lymphocy#e nuclei "he o#her poin# o' /iew

pos#ula#es an ac#i/e process ser/in. #o #ransmi# a Vhori=on#alX 'low o' .ene#ic in'orma#ion

and #o correc# cell 'unc#ionin. by means o' in#ra.enome res#ruc#urin.s


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97E 98L "hey ha/e helped #o disclose cer#ain mechanisms underlyin. #he essen#ial

immunodepressi/e e''ec# o' ioni=in. radia#ionE emphasi=in. #he dea#h o' in#erphase

lymphocy#es H17E 89E 97E 99L "he reproduc#i/e dea#h o' lymphocy#es also makes somecon#ribu#ion #o #his immunodepressi/e mechanism H1JE 97L

"hese au#hors s#ar#ed 'rom #he 'ac# #ha# an impor#an# proo' o' #he decisi/e role o'

lymphocy#e dea#hs in radia#ion lymphopa#holo.y is #he correspondence o' #he 3DE

ob#ained when #he whole body is immuni=edE 3D\UK Qy and #ha# in #he sys#em o'adap#i/e #rans'er o' lymphoid cellsE 3D\U[ Qy "his a prioricircums#ance con/inced

radiobiolo.is#s #ha# #he in#erphase and reproduc#i/e dea#h o' lymphocy#es is decisi/e in

de/elopmen# o' radia#ion immunopa#holo.y Ywhich we do no# 'ind incon#ro/er#ibleE since#his occurred be'ore our disco/ery o' #he phenomenon o' re/ersible redis#ribu#ion o'

biochemical parame#ers in #he blood-in#ers#ices-lymph-blood sys#em o' irradia#ed

animalsZ

Pur#hermoreE $D ]hi/o#o/skiy H1UL demons#ra#ed a Wuan#i#a#i/e associa#ion

be#ween #he pykno#ic chan.es in #he cell nuclei o' #hymocy#es and produc#ion o' produc#s

o' pos#radia#ion chroma#in decay "he en=yme responsible 'or #he decomposi#ion o'chroma#in in irradia#ed cells is Ca:M.-dependen# endonuclease !reas o' endonuclease

a##ack are dis#ribu#ed randomly and are no# associa#ed wi#h #he le/el o' repe#i#ion o'nucleo#ide seWuences o' D! or #he #ranscrip#ional ac#i/i#y o' chroma#in "his suppor#s

#he conclusion #ha# #he radia#ion dea#h o' lymphoid cells and #he .eneral biolo.ical

phenomenon o' pro.rammed cell dea#h are iden#ical in na#ure &oni=in. radia#ionE #husElike o#her lympholy#ic 'ac#orsE can e/oke induc#ion o' .roups o' speci'ic .enes #ha#

swi#ch on #he cell dea#h pro.ram Nowe/er some researchers H1UE 9ULE whoE includin.

ioni=in. radia#ion in #he .roup o' lympholy#ic a.en#sE wi#hou# su''icien# us#i'ica#ionE

ar.ue #ha# .lucocor#icoidsE c!M+ and alkyla#in. compoundsE which are so di''eren# inchemical na#ureE mus# en#er in#o speci'ic chemical in#erac#ions o' #he epi#ope-idio#ope

#ype wi#h #he speci'ic .ene loci responsible 'or cell dea#hE while ioni=in. radia#ion byna#ure is incapable o' direc#ly en#erin. in#o such in#erac#ion wi#hou# adduc#or-media#orsspeci'ic #o radia#ion "husE we ha/e pos#ula#ed #ha# hi.h-ener.y irradia#ionE like o#her

.eno#oxinsE can e/oke #he induc#ion o' speci'ic .enes #o swi#ch on #he cell dea#h pro.ram

only i' media#ed by a sys#em o' speci'ic adduc#ors "hese hypo#heses ha/e beencon'irmed in our researchE as well as elsewhere

4#udyin. #he #ri..er mechanism 'or radia#ion-induced lymphocy#e dea#hE &

4orokina H8[L used #he resul#s o' numerous experimen#s #o show #ha# ioni=in. radia#ion

induces chan.es in #he an#i.en pheno#ype o' imma#ure #hymocy#es in mice "his has #he

same #ype o' e''ec# as chemical di''eren#ia#ion induc#ors and #hymo#ropinE whichindirec#ly a##es#s #o #he speci'ic modi'yin. e''ec# o' ioni=in. radia#ion

Pundamen#al a##ainmen#s in molecular radiobiolo.y ha/e 'os#ered si.ni'ican#

pro.ress in explainin. #he mechanisms o' #his process and #his has permi##ed T+

Thanson #o approach unders#andin. o' many aspec#s o' #he occurrenceE de/elopmen# andreali=a#ion o' radia#ion e''ec#s in lymphocy#es H9UL Si#hin #he con#ex# o' #he proposed

hypo#hesisE in#erphase dea#h o' irradia#ed lymphocy#es is considered one o' #he examples

o' #he .eneral biolo.ical phenomenon o' pro.rammed cell dea#h &n#erphase cell dea#hoccurs as #he resul# o' swi#chin. on a speci'ic .ene#ic pro.ramE #he #ri..erin. o' whichE

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#he au#hor asser#sE may occur as #he resul# o' many si.nalsE amon. which are /arious

#ypes o' lympholy#ic a.en#s .lucocor#icoidsE alkyla#in. compoundsE c!M+E

di''eren#ia#ion induc#orsE and ioni=in. radia#ion

"husE in addi#ion #o con'irmin. #he radiobiolo.ical idea #ha# #he main reason 'or#he de/elopmen# o' lymphopenia is in#erphase and reproduc#i/e lymphocy#e dea#hE #he

resul#s we ha/e ob#ained a##es# #ha# #he 'ac#or o' slowed lymph #ranspor# also makes an

impor#an# con#ribu#ion #o de/elopin. lymphopenia YPi.ure 1ZE resul#in. in de/elopmen#o' a de'ici# in circula#in. lymphocy#es in #he lymph 'low "he ma.ni#ude o' #his

con#ribu#ion can reach 8U-9G^ dependin. on 3D and elapsed #ime a'#er irradia#ion

YPi.ure 7Z

ml)min.

L*MP+ #L", ( !+& ("%M

thousands)m illeg./

days/

#igure 0. 1hanges over time in lymph flo2 A/ and in number of lymphocytes $/ of

rabbits 2ith severe A%S.

G


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C&3CO0!"&% & "N< %3M

cells:hour

days7

#igure 3. 1hanges over time in circulation of lymphocytes and subpopulations in the

lymph-blood systems of rabbits 2ith severe A%S.

&'E alon. wi#h #he de/elopmen# o' #his processE we consider #he mi.ra#ion o'lymphoid cells #o #he wall o' lymphan.ions and an.ions Y#he 'i.ure shows #his #o in/ol/e

1U-1G^ o' #he lymphoid 'orms o' cellsZE ieE impairmen# o' #he speci'ici#y o' lymphocy#e

Vhomin.XE #hen #he in#erphase and reproduc#i/e dea#h o' lymphocy#esE and #hus #hisprocessE make a 9U-9G^ con#ribu#ion #o #he de/elopmen# o' lymphopenia "he increase

in #he #i#er o' au#o-an#ibodiesE #he morpholo.ical subs#ra#e 'or #he syn#hesis o' which islymphocy#e cellsE #he absence o' se/ere hyperpro#einemia in #he #ranspor# media in #he

irradia#ed animal_s body Ya'#er all #he dea#h o' any cell 'orms should be accompanied by.enera#ion o' pro#einE pep#idesE e#cZ and #he analysis o' #he chan.es o/er #ime in absolu#e

numbers o' lymphocy#esE #heir subpopula#ions Yand #heir ac#i/e capaci#y #o 'orm rose##es

wi#h sheep ery#hrocy#esE see Pi.ure 8Z and o' ery#hrocy#es and pla#ele#s all suppor# #hishypo#hesis

J


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#igure 4. !-theophylline tolerant lymphocytes of central lymph in cattle irradiated

at a dose of 3 5y, Scanning image. &nlargement 6 7888.

3esearch per'ormed by ! TirshinE winner o' #he O443 4#a#e +ri=eE and hisassocia#es be#ween 1IKJ and 1IIUE which unambi.uously demons#ra#ed #ha# black mo#leyca##le exposed #o radia#ion 'rom Chernobyl 'allou# exhibi#ed enhanced radia#ion

resis#anceE is par#icularly no#ewor#hy "hese s#udies con'irm #he principle underlyin.

radia#ion immuni=a#ion o' animals H18L

"he resul#s o' #his research ha/e si.ni'ican#ly con'irmed our hypo#hesis

concernin. #he speci'ici#y o' induc#ion o' #he radiobiolo.ical e''ec# %ur researchbe#ween 1IK7 and 7UU7 was de/o#ed #o s#udy o' #his area

%esearch materials and procedures

"hese s#udies were conduc#ed in #he $elarussian 4cien#i'ic and 3esearch &ns#i#u#e'or 3adiobiolo.y in QomelE #he 4# +e#ersbur. e#erinary &ns#i#u#eE #he Ta=an !ll-Onion

4cien#i'ic 3esearch e#erinary &ns#i#u#eE #he 0i#huanian e#erinary !cademy YTaunasZE

and &4< Y$onnE P3QE "oron#oE CanadaZ on black mo#ley ca##leE 7G-8U years o' a.eE li/ewei.h# o' 8UU-8GU k. Yn\189ZF Okrainian pi.sE UG-1U years o' a.eE li/e wei.h# 8G-IU k.

Yn\197ZF Vprekos X sheepE 8-17 mon#hs oldE li/e wei.h# 1K-78 k. Yn\1GJZF mixed breed

do.sE 7-9 years o' a.eE li/e wei.h# JU-JEG k. Yn\1J7ZE Chinchilla rabbi#sE 11-17 mon#hsoldE li/e wei.h# 8G-8[ Yn\1KUZE 0a#/ian dra'# horsesE 8-K years o' a.eE li/e wei.h# 8GU-

GGU k. Yn\87ZE $alp miceE 7-8 mon#hs oldE li/e wei.h# 7U-77 . Yn\7J8JZE Sis#ar ra#sE 8-9

mon#hs oldE li/e wei.h# 1KU-77U . Yn\9UU7Z "o exclude #he microbial 'ac#or in #he

pa#ho.enesis o' !34E #he experimen#s were per'ormed in .no#obio#ic animal labora#ories"o s#udy #he mi.ra#ional and #oxemic 'ac#or we used parabion#s wi#h crossed lymph and

blood circula#ion

"he experimen#al .roup consis#ed o' animals wi#h normal blood pro'iles and body

#empera#ureE in which #he homeos#a#ic cons#an# o' cen#ral lymph did no# exceed #he limi#so' normal /ariabili#yE which we had pre/iously de#ermined 'or 'i/e species o' mammals

Y"able 1Z since #his was o' 'undamen#al impor#ance #o our s#udy

[


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"able 1

+omeostatic constants of central lymph in animals

1onstant 1attle Pigs Dogs Sheep %abbits

C0 Yl:k.Z UU7[-UUK7 UU9U-UUIU UU8K-UU91 UU7U-UU[U UU9K-UU980ymph 'low

Yml:min:k.ZUU81-UU8J UU99-U 1JJ UU[1-UU[[ UU19-UUJG UU[J-UUKU

0eukocy#es Y#:`lZ 9I U7 J8 U9 7[ U7 G8 U8 8K U90ymphocy#es Y#:`lZ 9K U7 J1 U1 7G U7 G7 U7 8[ U8

-::- Y^Z IKU U8 IK9 UG IJU 1U IKJ UI IKU U9

?a -lymphocy#es Y^Z GJU 7J J8U 98 G8U 79 J1U 9U JJU 71?y -lymphocy#es Y^Z 7GU 7I 8UU 88 1KU 7U 1[U 91 8KU 1I? lymphocy#es Y^Z 1IU 71 J 1 17 17 1 18 G9 19 7J 7 77B -lymphocy#es Y^Z 89U 8U 89U 9K 8UU 89 8KU G1 7KU 1KMonocy#es Y^Z 18 U8 UI U9 8I 1U UJ U8 UI U7

eu#rophils Y^Z U8U8 U9 U7 U9 U7 U9 U8 UJ U7+la#ele#s Y#:`lZ I[U 1G K8U 17 JKU 77 1UUU 1J 88U 1[


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in #he experimen#al .roups o' animals "he animals were irradia#ed in 3OM-1[E +umaE

and +anorama de/ices "he exposure dose ra#e ran.ed 'rom 8 !:k. #o 7I !:k. %n #he

day precedin. radia#ion exposureE and also 1GE 8UE and 9G days pos#exposureE a lympho-/enous anas#omosis was crea#ed in #he animals usin. #he me#hod described in H8UL !

schema#ic dia.ram o' #he experimen#al procedure is pro/ided in Pi.ure 9

&6P&%M&(!AL M&!+"DS

#unctional Morpho-

logical

Surgical $io-

chemical

mmuno-

logic

%adioisotope

#igure 9. A schematic diagram of the e:perimental procedure 0 !horacic duct; 3.


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#igure = . Diagram of specific affine/ immuno-lympho-plasmasorption> 0-animal

lymphoplasma; 3, 9, = membranes 2ith immobili?ed ligands; 4 activated

charcoal; @ eluent.

1U


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#igure @. Direct e:tract of S%D 4 from central lymph (o. 9049. #irst hours after

irradiation in dose of =8 5y/.

"he speci'ici#y o' #he 43D was de#ermined #hrou.h #he reac#ions o' en=yme-linked

immonosorben# assay Y


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13/28

S$


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o' /arious epi#opes used a 43-7U YP3QZ &3 spec#rome#er usin. #he me#hod described in

H7J and 9KL

3adiomime#ic proper#ies o' 43D prepara#ions were e/alua#ed on #he basis o'

capaci#y #o induce radiobiolo.ical e''ec#s in #he animals a'#er #hey were adminis#eredparen#erally 0yophili=a#es o' 43D 1 and 43D 9:9 Yisola#ed 'rom #he lymph o' animals

irradia#ed a# doses inducin. cerebral and ex#remely se/ere !34Z were dissol/ed in an

iso#onic solu#ion o' aCl "he dose o' prepara#ion adminis#ered was based oncompu#a#ion o' #he amoun# o' 43D per uni# /olume o' cen#ral lymph and absorbed dose

o' radia#ion

4ymp#oms o' !34 induced wi#h 43D 1 and 43D 99 were compared wi#h similar

symp#oms induced by irradia#ion YPi.ure IZ

#igure 7. +orse (o. 09. &:tremely severe A%S @.= 5y/

"he resul#s o' #he s#udies were analy=ed usin. !%!

%esearch %esults

4ubs#ances isola#ed 'rom #he cen#ral lymph o' animals su''erin. 'rom #ypicalE.as#roin#es#inalE #oxic and cerebral 'orms o' !34 ha/e #he appearance o' li.h# bei.e #o

li.h# yellow powderE which adheres somewha# #o .lassE is soluble in wa#erE aWueous

solu#ions o' aClE and alcoholE and reac#s sli.h#ly #o Wuinoid radio#oxins eu#ral

aWueous solu#ions were used

19


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"able 7 presen#s #he componen#s o' 43D 8 and 43D 99 isola#ed 'rom #he cen#ral

lymph in #he .as#roin#es#inal and ex#remely se/ere 'orms o' !34 "he increase in le/el

o' absorbed dose 'rom #he #ypical 'orm o' !34 #o #he .as#roin#es#inal 'orm isaccompanied by a J-K^ .row#h in #he pro#ein and lipid componen#s and a s#able le/el o'

carbohydra#es "he mineral residue decreases by 7^ "he resul#s o' #he

chroma#o.raphic analysis re/ealed #he rela#i/e homo.enei#y o' #he 43D prepara#ionsE andaccordin. #o compu#a#ionsE #he molecular mass o' #he isola#ed de#erminan#s were on #he

order o' 7UU-7GU kDa "his circums#ance is responsible 'or 43D bein. #ranspor#ed

#hrou.h #he lympho.enic rou#e

"able 7

1omponents of S%D 4 and S%D 9)9

Componen# Y^Z &n#es#inal 43D 8 "ypical 43D 9:9

1 +ro#eins GU 1 UUI GJ7 U 17

7 0ipids 8K7 UU9 8U 1 UUI

8 Carbohydra#es 1U7 UU8 1U 1 UU[

9 Mineral residue 18 UU9 89 U 1[

"he &3-spec#ra o' #he prepara#ions showed bo#h #he .eneral and #he indi/idual

'ea#ures o' 43D &n par#icularE #he &3-spec#ra o' 43D 8 and 43D 9:9 su..es# #ha# bo#h#hese de#erminan#s are compounds o' iden#ical #ype "his was con'irmed by


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!s 'or #he mechanisms #hrou.h which #he conu.a#ed pro#eins we ha/e isola#ed

'orm a'#er radia#ion exposureE we ha/e #wo workin. hypo#heses

'reein. o' s#ored conu.a#ed pro#eins o' #his class #ha# were presen# earlierE'ollowed by #heir modi'ica#ionF

radia#ion-chemical and en=yma#ic processes responsible 'or new 'orma#ion o'

lipo-.lyco-pro#eins


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"ypical

Z ex#remely se/ere

g7U

g7U

7 1-77

7G-8U

7 1-77

1K-7U

1K-7U

bZ se/ere

g7U

g7U

g7U

77-7G

7J-8U

#'#-#'

1K-7U

cZ modera#e

g7U

g7U &

g7U

g7U

17U-71

7G-7J

9 9

7U-71

dZ mild g7U g7U g7U g7U

g7U

1K-7U

9

7G-8U

"hree #o 'i/e hours a'#er irradia#ion Y"able 9Z #ha# induced a mild 'orm o' !34E#here was an increase in le/el o' 43D 91 in #he lymph and blood Ya'#er J-7U hoursZ o'

irradia#ed animals #o #he maximum le/el 43D 91 remained a# #ha# pla#eau 'or G-7U

hours "he an#ibody #i#er #o 43D 9:1 in lymphoplasma and blood serum pre-irradia#ion

was 1KU-11UUE a##es#in. #o #he lack o' 43D 9:1 in #he animals_ bodies !'#er GU-JUhoursE #he an#ibody #i#er #o 43D 9:1 increased and reached a maximum on day 7G-9G "he

coe''icien# o' speci'ici#y ran.ed 'rom 7U-7G &n indi/idual animals #he an#ibody #i#er #o

43D 9:1 remained a# a rela#i/ely hi.h le/el un#il JU days and on a modera#e le/el wi#hC4 o' a# leas# 7 'or up #o 7 years Y#he dura#ion o' #he obser/a#ion periodZ should be

no#ed #ha#E alon. wi#h 43D 9:1 and #he an#ibodies #o i#E #he presence o' 43D 9:7 43D

9:8E and 43D 9:9 and #he correspondin. an#ibodies was de#ec#ed in all animal speciesE bu#in si.ni'ican#ly lower #i#ers YC4 \ 1G 1KZ

1[


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"able 9

!ime to develop ma:imum level of S%D as a function of type and severity of

acute radiation sicBness

"ype and se/eri#y o'

!34F 43D "ime in#er/al a'#er irradia#ion YhoursZ #o de/elop maximum 43Dle/elE animal species and irradia#ion subec#

3abbi#s Do.s Ca##le

lymph blood lymph blood lymph blood

"ypical mildE 43D 9:1 8- K J-1U G- K 7U-9U 8-17 J-1G

Modera#e 43D 9:7 8-1U J-1U 8-1U 1G-GU 8-19 K-1G

4e/ere 43D 9:8 8-79 J-79 1-[7 K-[7 8-79 J-[7


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immunochemical reac#ions in animals wi#h modera#e le/els o' !34 .enera#e less 43D

9:1 and more 43D 9:7E which is also demons#ra#ed by #he #i#er o' an#ibodies rela#i/e #o

#he de#erminan#E #he le/el o' whichE like #he le/el o' correspondin. an#ibody #i#ers showedmore indi/idual #o indi/idual #han species #o species /aria#ion

"husE #he blood serum o' cer#ain rabbi#s #ha# showed an earlier reac#ion o' ac#i/e

an#ibody de/elopmen# con#ained hi.h #i#ers o' an#ibodies #o 43D 9:1 and 43D 9:7E which

con#inued #o be obser/ed 'or #he en#ire 7-mon#h obser/a#ion period "he blood serum o'ca##le exhibi#ed hi.h an#ibody #i#ers only #o 43D 9:7 Y'rom 7 weeks #o 7 mon#hsZ and

some do.sE durin. #he ini#ial periodE exhibi#ed hi.h an#ibody #i#ers YC4\79Z #o 43D 9:1E

and subseWuen#ly #o 43D 9:7 Ylikewise persis#in. un#il mon#h 7Z

should also be no#ed #ha# animals whose blood and lymph con#ained hi.h #i#erso' 43D 9:7 and 9:1 a'#er irradia#ion showedE as well as hi.h an#ibody #i#ers #o #hese

subs#ances Y17UUK- 179KKZE did no# exhibi# ei#her o' #hese charac#eris#ics Yan#ibody #i#ers

were 1KU-11UUZ be'ore irradia#ion "he leadin. de#erminan# in #he .as#roin#es#inal

syndrome o' !34E as re/ealed by #he


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& I 973 nm.

)hours)

#igure 08. 1hanges over time in level of S%D 9)9 in the blood of dogs J,K/ and cattle

", / 2ith e:tremely severe A%S J, 2ithout &DL and K, " 2ith &DL.

Shen we compared #he #ime course o' 43D 9:9 'orma#ion in blood and lymph

wi#h #he #ime course o' lymph 'low in #he #horacic duc# we no#ed a correla#ion be#ween#hese processes "husE subs#an#ial shi'#s in lymph #ranspor# were no#ed 9K-[7 hours a'#er

irradia#ion and #he maximum concen#ra#ions o' 43D 9:9 in lymph and blood were no#ed

a# 8-1U and 8-1I hoursE respec#i/ely "hus #he ra#e o' 43D 9:9 inpu# in#o blood #hrou.h

lymph 'low durin. #he 'irs# 'ew hours a'#er irradia#ion is /ery si.ni'ican# !s #helymphos#a#ic process induced by radia#ion exposure e/ol/esE #here is a decrease in #he

le/el o' 43D 9:9 in blood

&n se/ere and ex#remely se/ere !34E in addi#ion #o 43D 9:8 and 9:9 and #he

correspondin. an#ibodiesE we always 'ound 43D 9:1E 43D 9:1 and #heir speci'ican#ibodies in #he animal_s lymph and blood Nowe/er #heir coe''icien#s o' speci'ici#y

ran.ed 'rom 1J-7U should be specially no#ed #ha# 43D 8 was presen# in #he lymph

and blood o' animals who ul#ima#ely died YT%]%Z and absen# in #hose who sur/i/edY"able 8Z

"husE #he hi.h le/els o' C4 alon. #he Vdia.onalX in "able 8E which s#ar#s wi#h a

mild de.ree o' !34 Yminimal doses o' radia#ion were used in #hese experimen#sZ and

ends wi#h #he cerebral !34 syndrome a##es#s #o a immunochemical reac#ion speci'ic #o

#he radiobiolo.ical e''ec# in #he ran.e o' !34 'orms s#udied

7U


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#igure 00. Sheep (o. $-8904. 00 days after administration of S%D 9)9 preparation.

Simulation of the clinical picture of e:tremely severe A%S sheep died on day 03/.

"he clinical physiolo.ical symp#oms here were shor#-#erm a.i#a#ion 'or #he 'irs# 7

hours a'#er adminis#ra#ion o' #he prepara#ion accompanied by 'i#s o' arrhy#hmiaE decreasein appe#i#e and increased peris#alsis 4hor#-#erm leukocy#osis .a/e way #o a pro.ressi/e

increase in leukopeniaE mainly a##ribu#able #o decrease in #he absolu#e number o'

lymphocy#esE minimal le/els o' which were 'ound be#ween days [ and 1G a'#er inec#ion!moun#s were 17-1J 1UUU:`l and U9-UG #housand:`l in sheep and 1K-7G #housand:`l

and UG-U[ #housand:`l in ca##le 3eco/ery o' absolu#e and rela#i/e le/els o' leukocy#esand lymphocy#es was obser/ed in some animals be#ween days 8U and JU

+la#ele# le/els exhibi#ed #hrombocy#openia accompanied by pro.ressi/eery#hrocy#openia Yin animals o' #he #hird experimen#al .roupZE which de/eloped in#o

anemia

!n ex#ensi/e blood analysis o' #he peripheral blood o' #he ca##le showed #ha# #he

processes induced by #he 43D 9:9 inec#ion and #he processes occurrin. a'#er irradia#ion

were o' #he iden#ical #ype H17E 99L

!nalysis o' #he de/elopmen# o' #he clinical reac#ion #o 43D 9:9 adminis#ra#ionEwhich was assessed on #he basis o' body #empera#ureE and hear# and respira#ion ra#eE

es#ablished #ha# all experimen#al animals showed reac#ions o' #he same #ype 'or all #he

#es#ed doses and #ha# sheep and horses were more sensi#i/e #o #he adminis#eredprepara#ion "husE in sheep in experimen#al .roup #hreeE which recei/ed 43D 9:9 in #he

maximum dose #es#edE 1 or 7 days be'ore dea#h body #empera#ure increased by 1G-7 f CE

reachin. 917f "his was accompanied by se/ere #achycardia and #achypneaE which weremeasured a# 1UG-1UJ and [U-KU per minu#eE respec#i/ely Shen 43D 9:9 was

adminis#ered in #he in#ermedia#e and maximum dose le/elsE sheep and ca##le showed

77


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chan.es o' #he same #ype bu# o' lesser de.ree "he maori#y o' experimen#al animals had

reco/ered be#ween days 8U-JU a'#er inec#ion o' #he prepara#ion

!u#opsy on #he animals #ha# died showed chan.es charac#eris#ic o' acu#e radia#ion

sickness accompanied by marked hemorrha.ia 4ome sheep showed areas o' epila#ion on#he back and abdomen

Comparison o' #he clinical pic#ure and #he chan.es re/ealed by au#opsy and

considera#ion o' #he #ime course o' animal dea#hs induced by 43D wi#h /arious epi#opes

and in /arious dosesE led us #o conclude #ha# isola#ed de#erminan#s 'rom cen#ral lymph o'animals irradia#ed in a broad ran.e o' doses mani'es# marked radiomime#ic e''ec#s

charac#eris#ic o' #he symp#oms o' acu#e radia#ion sickness o' one or ano#her 'orm

"husE #he research per'ormed su..es#s #ha# when animals are irradia#ed in doses

inducin. de/elopmen# o' cerebral Y1ZE #oxic Y7ZE .as#roin#es#inal Y8Z and #ypical Y9Z 'orms

o' acu#e radia#ion sicknessE #he radiobiolo.ical e''ec#s are o' #he na#ure o' a speci'icimmunochemical reac#ionE which #akes #he 'orm o' .enera#ion in #he lymphoid sys#em o'

a hi.h molecular mass MM 7UU-7GU kD! .lycopro#ein Y43DZ wi#h a speci'ic epi#ope 'oreach 'orm o' radia#ion inury Y43D 1F 7F 8F 9Z 4pecies and indi/idual radiosensi#i/i#y o'animals is de#ermined by #he indi/idual_s capaci#y #o respond #o radia#ion exposure by #he

'orma#ion o' #he dominan# speci'ic de#erminan# o' #he correspondin. epi#ope &n o#her

wordsE #he se/eri#y and 'inal resul# o' #he radiobiolo.ical e''ec# induced by #he iden#icalradia#ion dose in indi/iduals o' #he same or di''eren# animal species depends on which o'

#he .lycopro#ein epi#opes 'orms in #he body o' #he irradia#ed animal

Despi#e #he 'ac# #ha# #he pa#ho.enic mechanism underlyin. 'orma#ion o' #he

radiobiolo.ical e''ec# has been considered in #he li#era#ure since 1KIJE #heimmunochemical speci'ici#y o' #his mechanism has no# been in/es#i.a#ed un#il now

"he experimen#al con'irma#ion o' #his hypo#hesis o' #he speci'ici#y o' #heimmunochemical reac#ions underlyin. #he radiobiolo.ical e''ec#s supplied by #he presen#

s#udies has pro/ided us wi#h #he know how #o crea#e experimen#al samples o'

an#iradia#ion /accines and speci'ic means o' #herapy and dia.nosis o' radia#ion inuries


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"able Go Qroup j

species

4!

dose

Y`.:k.Z

&rrad

dose

YQyZ

umber o' days be'ore irradia#ion 4!

adminis#ered: +ercen# animals sur/i/in. 'or

8U days

G 1U 1G 8U JU

1 3a#s G

1U

1G

7U

7U

7U

7U

7U

1UU

1UU

1UU

1UU

KG

KG

IU

IU

IU

1UU

IG

IG

IU

1UU

1UU

IU

IU

IG

1UU

IG

KG

1UU

1UU

IU

Con#rol

Yradia#ion

onlyZ -- 7U 1UU U U U U U

7 3abbi#s G

1U

1G

7U

7U

7U

7U

7U

IG

IG

IG

IG

KU

IU

KG

KG

KU

1UU

IU

K YsicZ

KU

IG

1UU

IU

[G

1UU

1UU

KG

[U

1UU

1UU

KU

Con#rol

Yradia#ion

onlyZ -- 7U IG U U U U U

8 Do.s G

1U

1G

7U

7U

7U

7U

7U

JG

JG

JG

JG

[U

[U

JG

[U

[G

IG

IG

KU

KU

IG

1UU

[G

[U

1UU

IG

KU

[U

IG

1UU

IU

Con#rol

Yradia#ion

onlyZ -- 7U JG U U U U U

'ollows 'rom "able G #ha# #he maximum radiopro#ec#i/e e''ec# o' 4! occursa# doses o' 1U-1G `.:k. and adminis#ra#ion #imes 1U-JU days be'ore exposure #o le#hal

doses o' radia#ionE ensurin. sur/i/al ra#es o' IG-1UU^ in experimen#al animals

should be no#ed #ha# doses o' G or 7U `.:k. adminis#ered 1U-JU days be'ore

irradia#ion also had a hi.h radiopro#ec#i/e e''ec# Y[U-IU^ZE and adminis#ra#ion o' 4! G

and IU days be'ore irradia#ion ensured sur/i/al ra#es o' 9U Ysic no such number in#able"ransZ #o IU^ Pa#ali#y ra#e was 1UU^ in #he con#rol condi#ions


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7 3abbi#s


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a me#hod o' isola#in. #he Vradia#ionX an#i.enF

a me#hod o' usin. #he Vradia#ionX an#i.enF

possession o' know-how #o isola#e #he Vradia#ionX an#i.en

Se ha/e prepared #he 'irs# /olume o' a #hree-/olume mono.raph on V"he

3adiobiolo.y o' MammalsX

Se ha/e de/eloped procedural recommenda#ions on #he Viological Chemistry Moscow Medi#sinaE 1IK7E [GU

pa.es

J $i=hokasE ! Maliye/E M "he radia#ion an#i.en and speci'ic me#hods o'dia.nosis and #herapy R ;eterinaria ir ?ootechnika,@YsicZE 188G 7UU1E pp G-1U

[ ladimiro/E Q e# al %n low molecular mass D! in #he blood plasma o'

irradia#ed animalsMat' radiobiol' syeAdaE Tie/E 1II8E 1E p 1KJ

K Qru=de/E Q+ 1he 6cute one Marrow 5yndrome Moscow Medi#sinaE1IKKE 198 pa.es

I ]hdano/E D! Beneral 6natomy and Physiology of the 3ymphatic 5ystem

0enin.rad 1IJ7E 88J pa.es1U ]hi/o#o/skiyE $D Molecular mechanisms o' irradia#ion-induced pro.rammed cell

dea#h !u#hors abs#rac# o' disser#a#ion 'or doc#ora#e in biolo.ical sciences 0enin.radE

1IKKE 97 pa.es

7J


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81a Maliye/E ME +opo/E DE TirshinE ! e# al 1he Phenomenon of 5pecific

4mmunochemical

anti-rad vaccine. russia. kazan. 1990-1994 yy

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