Tritium radiobiological effects in mammals: review of experiments of the last decade in Russia.

This review briefly describes techniques and basic results of experimental investigations in mice and rats on metabolism, dosimetry, and radiobiological effects of tritium oxide and some tritiated biogenic compounds (glucose, amino acids, and nucleosides) during the last 10 to 15 years in Russia. The content of water in tissue cells of mammals is shown to be 15 to 40% less than in whole tissue. The kinetics of tritium incorporation from oxide (HTO) and its retention in DNA of hemopoietic tissues were studied. The contribution of bound tritium to dose strongly depends on the chemical form of tritium and reaches 90% when labeled L-lysine is injected. Specific features of the action of HTO on hemopoietic tissue were investigated in tests of damage and repair of DNA, induction of chromosome aberrations in cells, content of nucleic acids, kinetics of cell populations, immunity parameters, carcinogenesis, decrease of life span, induction of dominant lethal mutations in germ cells in male mice, and reciprocal translocations in mouse spermatogonia. According to these tests, the radiobiological effects of tritium beta radiation in the form of oxide is 2 to 6 times higher than for gamma radiation of 137Cs. The frequency of dominant lethal mutations induced by labeled lysine, thymidine, and deoxycytidine is 3 to 12 times higher than those induced by equal HTO activity. The results of these investigations are used to standardize HTO and the various biogenic compounds of tritium, improve techniques of indirect dosimetry, provide medical aid to personnel, and estimate population risk.

[Effect of mammalian and Escherichia coli DNA on rat somatic cell chromosomes]. / Vliianie DNK mlekopitaiushchikh i Escherichia coli na khromosomy somaticheskikh kletok krys

High-polymer DNA isolated from mammalian lymphoid tissues (rat spleen, calf thymus) and from Escherichia coli increases the frequency of quantitative lesions in bone marrow cells of normal Wistar rats. The highest percentage of aberrant metaphases was revealed 24 hours after the injection of mammalian DNA, the frequency of aberrations being 9 times higher than the control values after the injection of heterologous DNA and 6 times higher-after the injection of homologous DNA. The effect observed was not a prolonged one, and 72 hours following the DNA injection the numbers of aberrant cells decreased to the control level. The maximal frequency of aberrations in bone marrow cells of rats treated with bacterial DNA was found 72 hours after the injection, when a 4-fold increase above the spontaneous aberration level was observed. Definite differences in the character of structural changes of chromosomes induced by DNA of different origin were revealed. Mammalian DNA injected produced the chromatid-type aberrations only. The injection of bacterial DNA led to the formation of both chromatid and chromosome aberrations. Possible mechanisms of the increase of chromosome aberration frequency in rat somatic cells under the action of high-polymer DNA of different origin are discussed.

[Biochemical study of erythroid hematopoietic reserves during prolonged irradiation]. / Biokhimicheskoe izuchenie rezervnykh vozmozhnostei éritroidnogo krovetvoreniia pri dlitel'nom obluchenii.

A study was made of the effect of hydrochloride phenylhydrazine on the content and rate of biosynthesis of nucleic acids in the bone marrow and spleen of rats exposed to long-term fractionated gamma-irradiation (0.5 Gy, 6 times a week). The stimulatory effect of phenylhydrazine on the rate of the nucleic acid biosynthesis was shown to decrease in the tissues under study with dose cumulation from 2.5 to 25 Gy.

[Structure and repair of rat thymus DNA during long-term irradiation]. / Struktura i reparatsiia DNK vilochkovoi zhelezy krys pri dlitel'nom obluchenii.

During long-term fractionated irradiation (0.5 Gy, daily) the molecular weight of single-stranded DNA of the thymus of exposed rats remained the same as that of intact animals till the dose of 25 Gy had been cumulated. The integrity of the DNA structure was ensured by the repair of DNA and elimination of cells with unrepaired lesions. The role of repair decreased and the elimination of cells increased with increasing cumulative dose.

[Relative biological effectiveness of tritium oxide based on nucleic acid metabolic indices]. / Otnositel'naia biologicheskaia éffektivnost' okisi tritiia po pokazateliam metabolizma nukleinovykh kislot.

Relative biological effectiveness (RBE) of tritium oxide, as compared to gamma-rays (137Cs), with regard to LD50/30 is 2,32 +/- 0,69 for rats. The RBE coefficients for tritium oxide are obtained with regard to some indices of nucleic acid metabolism in the thymus and spleen during the dose formation (0-14 days). The RBE of tritium oxide increases with a decrease in radiation dose as determined according to the concentration and content of DNA per organ and activity of thymus DNAases.

[Incorporation of tritium into the DNA of hematopoietic tissues during prolonged administration of tritium oxide]. / Inkorporatsiia tritiia v DNK krovetvornykh tkanei pri dlitel'nom vvedenii okisi tritiia.

With long-term (90 days) administration of tritium oxide (0.37 MBq/g body weight) to ras the carbon-bound tritium accumulated in DNA of haemopoietic tissues during two-month administration of the isotope (the accumulation half-time of 15-25 days); during the next month, the isotope level remained nearly constant (about 20 X 10(6) decay/min/g DNA). Elimination of tritium from DNA started 3 days after termination of its administration and proceeded with two half-times (4-8 days and 12-18 days). The ratio of the tritium content per 1 M hydrogen of DNA to tritium content per 1 M hydrogen of tissue water increased up to 0.5-0.7 during the uptake of tritium oxide, and up to 4-7 after the administration of the isotope had ceased.

[Dependence of the damage and recovery of nucleic acid metabolism on the dose rate in tritium oxide exposure]. / Zavisimost' porazheniia i vosstanovleniia metabolizma nukleinovykh kislot ot moshchnosti dozy pri deistvii okisi tritiia.

Disturbance and normalization of nucleic acid metabolism in rat thymus was studied after the effect of tritium oxide delivered in similar cumulative doses but at different dose rates. Both the disturbance and normalization were shown to be a function of dose rate, the slightest damage and the complete recovery being registered at the lowest dose rate (the amount of tritium oxide administered being 0.37 MBq/g/day). The rate of restoration was also a function of dose rate; with tritium oxide dose of 1.85 MBq/g/day (the dose rate at the stage of the equilibrium tritium content in the aqueous phase being 0.38 Gy/day) it was 9 times as high as that after a dose of 0.37 MBq/g/day (0.11 Gy/day dose rate).

[Effect of tritium oxide in a wide range of doses on the nucleic acid metabolism of the rat spleen]. / Vliianie okisi tritiia v shirokom diapazone doz na metabolizm nukleinovykh kislot selezenki krys.

A single injection of tritium oxide in a dose of 1.1 MBq/g (0.5 Gy for 30 days) was shown to impair the nucleic acid metabolism in the rat spleen. The changes in the indices under study (e.g. mass, nucleic acid content and biosynthesis) increased with the dose, and the recovery started later and was incomplete. Qualitative differences were found in the effects of tritium oxide and gamma radiation with regard to the rate of DNA biosynthesis: 24 h following the injection of the radionuclide specific activity of DNA increased with dose, whereas this function was inverse in the case of gamma irradiation as it was reported in the literature.

[Characteristics of nucleic acid biosynthesis in the activation of erythroid cell proliferation due to prolonged gamma irradiation]. / Osobennosti biosinteza nukleinovykh kislot pri aktivatsii proliferatsii éritroidnykh kletok, vyzvannoi dlitel'nym gamma-oblucheniem.

Most important differences were detected in the nucleic acid metabolism in the rat spleen with increasing proliferation of erythroid cells under the effect of long-term gamma-irradiation and acute hemolytic anemia. It is assumed that humoral regulation pathways and molecular mechanisms of changes in erythropoiesis depend upon haemopoietic stem cell pool.

[Structure of DNA from the rat thymus during prolonged exposure to tritium oxide and external gamma-irradiation]. / Struktura DNK vilochkovoi zhelezy krys pri dlitel'nom vozdeistvii okisi tritiia i vneshnego gamma-oblucheniia.

Thymus depopulation, DNA destruction as estimated according to the level of single-stranded breaks (SSB) and DNA structural derangement revealed by the viscosimetric assay of alkaline lysed thymocytes were observed in the course of a prolonged (1 mos) radiation exposure to tritium oxide (the 1st group) and equidimensional external gamma-irradiation (the 2nd group) in a summary dose of 10 Gy in rats. Depletion and destruction were 1.5-2 times more pronounced in case of HTO exposure. A study of the repair has revealed an increase in the number of hardly repairable or irrepairable breaks by the end of the study: by the 25th day the number of SSB repaired after additional test irradiation was O and 30% in the rats of the 1st and 2nd groups respectively.

[Damage to the structure of DNA and to the metabolism of nucleic acids in the thymus in relation to the dose of tritium oxide]. / Povrezhdenie struktury DNK i metabolizma nukleinovykh kislot timusa v zavisimosti ot dozy okisi tritiia.

Single administration of tritium oxide (1.1-44 MBq per 1 kg of body mass) causes a dose-dependent decrease in the level of rat thymus nucleic acids within the range of concentrations of injected tritium 5.5-44 MBq/g. Biosynthesis of nucleic acids turned out to be more sensitive to tritium oxide action. The rate of biosynthesis changed on the 1st day at the lowest dose of 1.1 MBq/g, the absorbed dose on the 1st day was 7.5 cGy. Dose-dependent disorders of DNA structure in the content of 2-strand DNA after the administration of tritium oxide (9-44 MBq/g) were established.

[Study of the structure and metabolism of the rat thymus gland during long-term administration of tritium oxide in different doses]. / Izuchenie struktury i obmena nukleinovykh kislot vilochkovoi zhelezy krys pri dlitel'nom vvedenii okisi tritiia v raznykh dozakh.

During-3-month administration of tritium oxide (0.37, 0.925 and 1.85 MBq/g body weight) to rats one could observe the loss of the thymus weight, decrease in the concentration, content and production of DNA and RNA per organ, reduction of the molecular weight of single-stranded DNA, increase in the content of the salt-soluble polydeoxyribonucleotides, and activation of acidic DNAases. These changes were function of tritium dose daily administered to rats.

[Changes in the structure and metabolism of rat thymus nucleic acids following cessation of long-term administration of different doses of tritium oxide]. / Izmeneniia struktury i metabolizma nukleinovykh kislot vilochkovoi zhelezy krys posle prekrashcheniia dlitel'nogo vvedeniia okisi tritiia v raznykh dozakh.

A study was made of the processes of restoration of metabolism and nucleic acid indices in rat thymus after the cessation of the long-term administration of various doses of tritium oxide. The restoration of the indices under study was only observed after tritium dose of 0.37 MBq(g.day)-1. At higher doses, 0.925 and 1.85 MBq(g.day)-1 the recovery was transient and the indices changed again.

[Comparison of the biological effects of tritium oxide and gamma radiation based on changes in the mass of the rat thymus gland]. / Sravnenie biologicheskogo deistviia okisi tritiia i gamma-oblucheniia po izmeneniiu massy vilochkovoi zhelezy krys.

RBE of tritium oxide (cumulative doses from 0.33 to 14.7 Gy), in comparison with gamma-radiation, amounted to 2-3 as estimated by the thymus mass. As determined by the rate of injury and repair, the RBE values decreased from 4 to 1.4 with dose increasing, and from 6.5 to 1.3, by the periods of half-decrease and half-recovery of the organ mass. The 2-3-fold variations in the RBE values for various parameters of the organ mass changes were registered at low doses, whereas within the range of median and high doses under study, the differences were insignificant.

[Comparison of the structure and catabolism of rat thymus DNA exposed to tritium oxide and gamma-radiation in equal doses]. / Sravnenie struktury i katabolizma DNK vilochkovoi zhelezy krys pri deistvii okisi tritiia i gamma-oblucheniia v ravnykh dozakh.

A decrease in DNA concentration and in the molecular mass of single-stranded DNA, an increase in the PDN content, and activation of acid DNAses in rat thymus were observed after a single administration of tritium oxide in a dose of 22 mBq/g (a cumulative dose of 7.8 Gy) and gamma-irradiation at a corresponding dose-rate and value of the cumulative dose. These changes were most pronounced during the period of dose accretion, i.e. during 14-30 days after the beginning of irradiation. The degree to which the indices under study varied from the controls was 2-3 times in rats given tritium oxide than in those exposed to gamma-irradiation.