ABSTRACT
The time-and dose-dependent changes ofFe3+-transferrin (Fe3+-TF) and Cu2+-ceruloplasmin (Cu2+-CP) pools, superoxide dismutase activity and the inhibitory activity of a2-macroglobulin in blood as well as changes in biosynthesis rates of deoxyribonucleotides, DNA and proteins in organs (spleen, liver, bone marrow, thymus) of mice and dogs total body irradiation have been studied, using ESR spectroscopy, radioisotope techniques and biochemical determination of enzymatic activity. The experimental data have allowed revealing the sequence of organism's response reactions against irradiation and their modifications by radioprotectors. Changes in blood Fe3+-TF pool is one of the most informative, highly radiosensitive and rapidly reactive marker against irradiation and drug administrations. This iron-transport protein controls a ratelimiting iron-dependent stage for DNA synthesis - the synthesis of dNTP,
V.L.Sharygin,M.K.Pulatova,T.G.Shlyakova,andI.N.Todorov327
catalyzedbyiron-containingribonucleotidereductase(Fe3+-RR).Itisshown thattime-dependentpost-irradiationchangesofFe3+-TFpoolinbloodare characterizedbythreedistinctstages:1)thepromptincreaseofpool(SOS-type response)playingtheimportantroleinprotectingcellgeneticapparatusfrom damage;2)thedecreaseofitspoolwithin3-18hafterirradiationresultingin thelossofFe3+-RRactivityintissuesofblood-formingorgansthatmakemore strongerradiation-induceddamage;3)thefollowingphase-dependentincrease inFe3+-TFpoolatthe2nd,6thand10-1ihdaysafterirradiationduetoan increaseintransferrinsynthesis.Thisincreasemaybeconsideredasa compensatoryreactionofblood-formingorgansaimedatrestoringbloodand organcells.Thetime-dependentcoursesofthereactionsareindependentof radiationdosesindicatingtheuniversalandnonspecificresponseofthe organismagainstirradiation.Hence,theintensityofthiscompensatory-adaptive responseatthe2ndand6thdaysincreaseswithradiationdosetothelethallevel, andtheorganismresponsebecomesabnormalandphysiologicallyhypertrophic. Theprolonged"stressfulsyndromeofbiochemicaltensestate"shouldbe attributedtonegativeeffectsfortheorganism,sinceitmayresultinthefailure ofcompensatoryadaptiveorganismreactionsandanimalkilling.The radioprotectorspreventoccurrenceofthisdangerousstate.Dogswithinitial individualcharacteristicsofbloodwhichweretypicalof"suppressed"or "activated"stateshadabnormalresponsetoirradiationbylowdosesof0.25or 0.5Gy.Inthesecases,theintensityoforganismresponsereactionswas essentiallyincreasedandmarkedlydeviatedfromlineardosedependence.The phase-dependentincreaseofFe3+-TFpoolinbloodinpost-irradiationtime resultedintheincreaseofFe3+-RRactivityinblood-formingorgans.Thekey eventensuringthedevelopmentofcompensatoryadaptivereactionsisthe increaseofcapacityofprotein-synthesizingapparatus,theactivationof biosynthesisofdNTPandDNAagainstthetreatmentbydamagingfactors.
