Dependence of the damage and recovery of nucleic acid metabolism on the dose rate in tritium oxide exposure

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).     

Relative biological effectiveness of tritium oxide based on nucleic acid metabolic indices

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.     

Normal killer function in CBA mice as affected by long-term intake of tritium oxide

A study was made of the cytotoxic function of normal killers of CBA mice during long-term administration of tritium oxide in potable water (a cumulative absorbed dose of 8.7 Gy, dose-rate, 4.5 Gy/day) and at different times after termination of the radionuclide injection. A mean decrease of 20-30% in the lytic effect of the effectors from spleen of the experimental mice on cell-targets of K-562 human erythroleukosis was demonstrated by a 17-19-hour test with 51Cr. At later times after termination of action of tritium oxide, the cytotoxic effect of normal killers increased by 1.8 times as compared to intact controls of the same age.     

Incorporation of tritium into the DNA of hematopoietic tissues during prolonged administration of tritium oxide

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.     

Nucleic acid metabolism in rat liver after single and prolonged exposure to tritium oxide

It was shown that after a single administration of tritium oxide in a dose of 22.2 MBq/g body mass the liver mass increased, the concentration of nucleic acids decreased and the biosynthesis rate increased during a one-month observation. By the end of the observation period (the first year) the parameters under study were normalized. The long-term administration of tritium oxide in daily doses of 0.37, 0.925 and 1.85 MBq/g body mass caused changes in the nucleic acid metabolism which were less manifest (at early times), than in the case of a single injection. At the same time, the long-term administration of tritium oxide in the dose of 0.925 MBq/g caused a substantial disturbance of the nucleic acid metabolism at later times (after 2-9 months).     

Increase in the activity of nuclear DNA polymerases in the tissues of mice subjected to long-term gamma irradiation

Activity of nuclear DNA-polymerase in the liver, lung and spleen tissues of mice subjected to long-term chronic gamma-irradiation (1.3 mGy/h) has been investigated. Chronic gamma-irradiation with a cumulative dose of 1.7 Gy during 55 days raises DNA polymerase activity in the irradiated tissue nuclei. Analysis of DNA-polymerase activity in the liver nuclei have demonstrated that this increase is connected with activation of DNA-polymerase beta.     

Inactivation of non-syngeneic hematopoietic stem cells by mouse lymphocytes after long-term exposure to tritium oxide

A study was made of functional activity of lymphocytes, which inactivated nonsyngeneic colony-forming units (CFU) in allogenous and xenogenous interaction systems, at different times after long-term action of tritium oxide in a cumulative dose of approximately 9 Gy. The function of these lymphocytes was depressed during the first months after termination of exposure while at later times it exceeded the control level. The consequences of the interaction between lymphocytes and nonsyngeneic CFU were also studied in this work.     

The significance of immunity disorders in the development of tumorous effects during the long-term action of tritium in mice

In experiments with CBA mice it was shown that the long-term influence of tritium oxide administered with drinking water daily during 180 days (370 kBq.g-1 of body mass, cumulative dose 8.7 Gy, dose rate 4.5 cGy.day-1) causes the development of immunity deficiency 90 days after the onset of the administration that persists for up to 270 days. There is a 34% decrease in the average life of irradiated animals and an increase in the number of malignant neoplasms (postmortem examination was performed after natural death or killing on days 250, 350 and 450). There is a direct relationship between the occurrence of malignant neoplasms and the immunity deficiency.     

The radioprotective efficacy of karotinil under acute external and internal irradiation]

Radioprotective, with respect to the whole body and reproductive system, geroprotective and anticarcinogenic properties of carotinyl after single acute external gamma-irradiation or exposure to tritium oxide have been revealed. It is concluded that the use of beta-carotene-containing substances is highly promising in preventing remote effects of chronic irradiation at low rates of absorbed doses, particularly the effects of incorporated radioactive substances.     

Cloning of murine B- and T-lymphocytes in vitro after the long-term action of tritium oxide

The cloning method was used to study the content of B- and T-lymphocyte committed precursors in central and peripheral organs of the immune system of mice at different times after long-term exposure to tritium oxide (a cumulative dose of approximately 9 Gy). It was shown that recovery of the colony-forming ability of the committed lymphocyte precursors was different in central and peripheral lymphoid organs; the dynamics and degree of restoration of the pools of B--(CFU--LB) and T--(CFU--LT) lymphocyte precursors were different.     

The immunity indices of rats after the long-term action of tritium oxide or gamma irradiation

In experiments with Wistar rats, a study was made of the content of antibody-forming cells and cytotoxic activity of normal killers after long-term administration of tritium oxide (3HOH) (370 kBq.g-1 of body mass daily, cumulative dose, 8.1 Gy, and dose rate, 8.5 cGy/day), and after gamma irradiation with corresponding doses. The long-term radiation effect caused a decrease in the immunity indices: the impairment of the immune reactions was more pronounced after the effect of 3HOH than after gamma irradiation. Damages to the immune system of mice and rats after irradiation with similar doses were compared.     

Assessment of relative biological effectiveness of tritium using chromosome aberration frequency in human blood lymphocytes

The aim of this work is to determine Relative Biological Effectiveness (RBE) of tritium beta-irradiation using chromosome aberration frequency in peripheral blood lymphocytes after radiation exposure in vitro and in vivo. The results of the experimental estimation of tritium beta-irradiation RBE in comparison with 60Co gamma-irradiation using analysis of unstable chromosome aberration frequencies in peripheral blood lymphocytes in reference to concrete conditions of the investigation were presented. It was demonstrated that tritium beta-irradiation is in total more effective than gamma-irradiation up to 1 Gy. RBE of tritium beta-irradiation was determined as 2.2 at minimum doses and decreased at higher doses (1 Gy) up to 1.25. For the first time results of the comparative analysis of frequencies of stable chromosome aberrations in two groups of professional nuclear workers (town Sarov) exposed to chronic tritium beta- and gamma-irradiation in remote period were presented. The grater RBE of tritium beta-irradiation was demonstrated. It has been estimated as 2.5.     

Effect of tritium oxide in a wide range of doses on the nucleic acid metabolism of the rat spleen

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.     

Metabolism of organically bound tritium in man

The classic methodology for estimating dose to man from environmental tritium assumes that all tritium, whether organically bound or free, enters directly into man's free body water compartment and is uniformly distributed as tritiated water. This methodology ignores the fact that organically bound tritium in foodstuffs may be directly assimilated in the bound compartment of tissues without previous oxidation. A four-compartment model consisting of a free body water compartment, two organic compartments, and a small, rapidly metabolizing compartment is proposed. The utility of this model lies in the ability to input organically bound tritium directly into organic compartments representing tissue solids. The model will be used to illustrate the potential importance of organically bound tritium to cumulative dose estimates. It is found that organically bound tritium in foodstuffs can increase cumulative total body dose by a factor of 1.7-4.5 times the free body water dose alone, depending on the bound-to-loose ratio of tritium in the diet.     

Study of the structure and metabolism of the rat thymus gland during long-term administration of tritium oxide in different doses

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.     

Granulocytopoiesis during the development of radiation injury from prolonged intake of tritium oxide

During chronic exposure to tritium oxide (a dose rate of 0.125 Gy/day-1, and a cumulative-absorbed dose of 22.1 Gy) different granulocytopoiesis compartments (i.e. polypotent CFUs, committed CFUc; proliferating, maturing, and functional pools) were differently damaged by radiation. In the course of the development of tritium oxide-induced affection granulocytopoiesis proceeds at an intense pace.     

Contents of extracellular DNA in blood of irradiated rats]

Intact rat plasma contains high-molecular DNA which moves as a single fraction in 0.5% agarose electrophoresis. As early as 2-5 hours after gamma-irradiation in a dose of 1-100 Gy there appears low-molecular DNA (about 180 nucleotide pairs), the amount of which directly correlates with the irradiation dose 5 hours after the exposure. Blot-hybridization showed that low-molecular DNA has no common nucleotide sequences with high-molecular DNA, though has sites similar to genome repeat sequences.     

Comparative evaluation of the carcinogenic effects of chronic exposure to tritium oxide and external gamma-radiation

In experiments of on rats a study was made of late effects of chronic action of tritium oxide (3HOH) during 6 months (37 X 10(4) Bq/g/day) and external gamma-radiation (137Cs) which were delivered in comparable daily and cumulative doses. It was shown that 3HOH produced a more pronounced blastomogenic effect. The RBE coefficient of tritium oxide approximated 1, with a reference to the average life shortening, and 4.2 and 2.5, with a reference to the incidence of malignant tumors and leukoses, respectively.     

Nucleic acid metabolism in rat hematopoietic tissues during and after prolonged administration of different doses of tritium oxide

During the long-term administration to rats of tritium oxide in doses of 0.37, 0.925 and 1.85 MBq/g body mass the content of karyocytes and nucleic acids in the bone marrow and spleen was decreased, the rate of their biosynthesis changed, the DNA structure impaired, the content of salt-soluble polydeoxynucleotides increased, and DNAases activated. The observed changes were function of dose. After the end of the administration of the isotope the animals which had received a lesser tritium dose exhibited a more rapid and complete recovery.     

Comparison of the biological effects of tritium oxide and gamma radiation based on changes in the mass of the rat thymus gland

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.