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).     

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.     

Comparison of three inbred lines of mice by overall and genetic radiosensitivity

The radiosensitivities of three mouse strains (BALB/cLacY, C3H/SnY, and 101/HY) have been compared using the following parameters: survival after irradiation at a dose of 6-7 Gy, chromosome aberration frequency in bone marrow cells after irradiation at a dose of 1.5 Gy, and the change in testis weight and frequency of abnormal sperm heads (ASHs) after irradiation at doses from 0.5 to 4 Gy. Strain BALB/c is the most radiosensitive with respect to the survival and chromosome aberration frequency in the bone marrow but the most resistant with respect to the change in testis weight and the frequency of abnormal sperm heads. Strain 101/HY was the most resistant with respect to survival and chromosome aberration frequency in bone marrow after irradiation but the most radiosensitive with respect to testis damage.     

Comparison of the structure and catabolism of rat thymus DNA exposed to tritium oxide and gamma-radiation in equal doses

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.     

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.     

Comparison of Three Inbred Mouse Strains with Respect to General and Genetic Radiosensitivity

The radiosensitivities of three mouse strains (BALB/cLacY, C3H/SnY, and 101/HY) have been compared using the following parameters: survival after irradiation at a dose of 6–7 Gy, chromosome aberration frequency in bone marrow cells after irradiation at a dose of 1.5 Gy, and the change in testis weight and frequency of abnormal sperm heads (ASHs) after irradiation at doses from 0.5 to 4 Gy. Strain BALB/c is the most radiosensitive with respect to the survival and chromosome aberration frequency in the bone marrow but the most resistant with respect to the change in testis weight and the frequency of abnormal sperm heads. Strain 101/HY was the most resistant with respect to survival and chromosome aberration frequency in bone marrow after irradiation but the most radiosensitive with respect to testis damage.     

Occurrence of mammary tumors in rats after exposure to tritium beta rays and 200-kVp X rays

The RBE for tritium was estimated in reference to 200-kVp X rays, using acceleration of breast tumor appearance in the female Sprague-Dawley rat as the end-point. Chronic X-ray doses of 0.3-2.0 Gy were delivered over 10 days. Intraperitoneal injections of tritiated water ranging in concentrations from 45 to 370 MBq/100 g body wt were administered, followed by four additional injections at 2-day intervals and half of the initial concentrations. Seventy-five percent of the total tritium dose was delivered to the mammary gland within the first 10 days and 95% within the first 20 days after the start of the tritium exposure. RBE estimations were based on various criteria including the tumor incidence per Gy at 450 days postirradiation and the time required to induce tumors in 50% of the animals at risk. The results suggest that tritium beta rays are about 1.1-1.3 times more effective than chronic 200-kVp X rays for acceleration of the appearance of rat mammary tumors. However, the uncertainties involved in these calculations are such that the effects of tritium beta rays could not be reliably distinguished from those of chronic 200-kVp X rays. Measured differences in RBE values were slightly larger for the comparison between acute and chronic X rays than for the comparison between chronic tritium beta rays and chronic X rays.     

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.     

Estimation of relative biological effectiveness of tritium according to chromosome aberration frequency in human blood lymphocytes

The goal of this work was to determine the relative biological effectiveness (RBE) of tritium β-radiation according to the chromosome aberration frequency in the peripheral blood lymphocytes after in vitro and in vivo radiation exposures. The experimental RBE assessment of tritium β-radiation relative to ⁶⁰Co γ-radiation according to unstable chromosome aberration frequency in the peripheral blood lymphocytes under particular conditions is described. It has been demonstrated that tritium β-radiation is, in general, more effective in the dose range of up to 1 Gy, which is most pronounced at low doses. The RBE value of tritium β-radiation at minimum doses reached 2.2 and decreased at higher doses (1 Gy) to 1.25. The data on comparative analysis of the frequency of stable chromosome aberrations in the blood lymphocytes of professional nuclear workers (Sarov, Russia) after long-term chronic exposure to tritium β-radiation, as compared with γ-irradiation, are reported for the first time. The higher biological effectiveness of tritium β-radiation was demonstrated and was estimated as 2.5.     

The early changes in humoral immunity under the prolonged action of tritium oxide with different dose rates

Within the dose range from 0.2 to 1 Gy, early changes in the humoral immunity of mice exposed to tritium oxide at varying dose rates have been investigated. The study of the immunity impairment at different stages of immunopoiesis permits to reveal the points (a lymphocyte precursor department) that are mostly affected by radiation, to find the causes of the decrease in the antibody production, and to reveal the relationship between the damages observed the dose absorbed and dose rate of beta radiation.     

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.     

Reciprocal translocations in germ cells of male mice receiving external gamma-irradiation

Data reported in the literature up to 1985 on reciprocal translocation induction in male mouse germ cells by external gamma-ray doses ranging from 0.5 to 6.0 Gy delivered at fixed dose rates were analyzed. On the assumption of a non-threshold linear dose response, zero effect at zero dose, and a center of distribution lying on an approximately straight line, calculations were made of linear regression coefficients. These coefficients (b), as a function of the dose rate (P), were well fitted by two straight lines: b = (3.15 +/- 0.59 log P) X 10(-6) for dose rates from 0.01 to 0.1 mGy/min; and b = (7.52 +/- 3.86 log P) X 10(-6) for dose rates ranging from 0.06 to 1.2 X 10(3) mGy/min. The intersection point of these two lines determined the so-called threshold level of the dose rate, namely, 4.6 X 10(-2) mGy/min, at which the effectiveness of external gamma-irradiation is not expected to exceed 2.36 X 10(-6)/mGy. In addition, experiments were undertaken in which yields were recorded of reciprocal translocations in germ cells of male mice exposed to 0.9 Gy of gamma-radiation at dose rates ranging from 6.14 X 10(-3) to 6.14 X 10(2) mGy/min (6 levels); comparisons were made with data published up to 1985 from similar studies using other fixed doses. To do this, translocation yields were expressed as relative yields (F) and their relationship to the dose rate (P) for the individual fixed doses was represented by an equation of the type: F = alpha + beta log P. For most of the equations, the regression coefficients were in good agreement and a single relationship was obtained to represent them. From the analysis performed it follows that, within the 0.6-6.0 Gy dose range, the pattern of the F vs. P relationship is unaffected by the dose. This supports the initial assumption that for the dose range up to 6.0 Gy the dose response for the reciprocal translocation yield is a non-threshold straight-line relationship.     

The relative biological effectiveness of low doses of 14 MeV neutrons in steady-state murine spermatogenesis as determined by flow cytometry

The relative biological effectiveness of 14 MeV neutrons in the low-dose range < or =1 Gy has been determined in differentiating and differentiated spermatogonia. Male NMRI mice were exposed to single doses of 2 cGy to 3 Gy of (60)Co gamma rays or neutrons. The ratios of testicular S-phase cells, 4c primary spermatocytes, and elongated spermatids were quantified by DNA flow cytometry 2 to 70 days after irradiation and were found to decrease. Histological samples and testis weight were analyzed in parallel. Doses of 2-5 cGy neutrons and 10-50 cGy gamma rays significantly (P<0.05) decreased the proportions of S-phase cells, spermatocytes and elongated spermatids at 4, 14 and 28 days postirradiation. For S-phase cells, the biphasic shape of the cell survival curves was described with a D(50) of 5 cGy neutrons. The D(50) for (60)Co gamma rays and the relative biological effectiveness could not be determined. The relative biological effectiveness of neutrons at 50% reductions of testis weight, primary spermatocytes, and elongated spermatids were 2.5, 10.0 and 6.1, respectively. This in vivo assay is interesting because of its sensitivity at dose ranges that are relevant for exposures in the environment, the workplace and radiotherapy.     

Reaction of mouse hematopoietic stem cells on gamma-irradiation and exposure to tritium oxide

In experiments on 600 mice, relative biological effectiveness of tritium oxide was compared to that of gamma-radiation (137Cs) with respect to the response of CFUc. It was shown that RBE of tritium oxide was 1 within the dose range from 0.8 to 0.4 Gy.     

Radiosensitivity of human bone marrow granulocyte-macrophage progenitor cells and stromal colony-forming cells: effect of dose rate

Study of the radiation biology of human bone marrow hematopoietic cells has been difficult since unseparated bone marrow cell preparations also contain other nonhematopoietic stromal cells. We tested the clonogenic survival after 0.05 or 2 Gy/min X irradiation using as target cells either fresh human bone marrow or nonadherent hematopoietic cells separated from stromal cells by the method of long-term bone marrow culture (LTBMC). Sequential nonadherent cell populations removed from LTBMC were enriched for hematopoietic progenitors forming granulocyte-macrophage colony-forming unit culture (GM-CFUc) that form colonies at Day 7, termed GM-CFUc7, or Day 14 termed GM-CFUc14. The results demonstrated no effect of dose rate on the D0 or n of fresh marrow GM-CFUc (colonies greater than or equal to 50 cells) after plating in a source of their obligatory growth factor, colony-stimulating factor (CSF) (GM-CFUc7 irradiated at 2 Gy/min, D0 = 1.02 +/- 0.05, n = 1.59 +/- 0.21; at 0.05 Gy/min, D0 = 1.07 +/- 0.03, n = 1.50 +/- 0.04; GM-CFUc14 at 2 Gy/min, D0 = 1.13 +/- 0.03, n = 1.43 +/- 0.03; at 0.05 Gy/min, D0 = 1.16 +/- 0.04, n = 1.34 +/- 0.05). There was a decrease in the radiosensitivity of GM-CFUc7 and GM-CFUc14 derived from nonadherent cells of long-term bone marrow cultures compared to fresh marrow that was observed at both dose rates. In contrast, adherent stromal cells irradiated at low compared to high dose rate showed a significantly greater radioresistance (Day 19 colonies of greater than or equal to 50 cells; at 2 Gy/min, D0 = 0.99 Gy, n = 1.03; at 0.05 Gy/min D0 = 1.46 Gy, n = 2.00). These data provide strong evidence for a difference in the radiosensitivity of human marrow hematopoietic progenitor compared to adherent stromal cells.     

P21(Cip1/WAF1) expression in the mouse testis before and after X irradiation

During spermatogenesis, the radiosensitivity of testicular cells changes considerably. To investigate the molecular mechanism underlying these radiosensitivity differences, p21^(Cip1/WAF1) expression was studied before and after irradiation in the adult mouse testis. P21^(Cip1/WAF1) is a cyclin-dependent kinase inhibitor (CDI) and has a role in the G1/S checkpoint and differentiation. P21^(Cip1/WAF1) expression was observed in the normal testis, using Western blotting analysis. After a dose of 4 Gy, but not after 0.3 Gy, an increase in p21^(Cip1/WAF1) expression could be determined in whole testis lysates. To investigate which germ cells are involved in p21^(Cip1/WAF1) protein expression, immunohistochemical analysis was performed on irradiated testis. In the normal testis a weak staining for p21^(Cip1/WAF1) was found in pachytene spermatocytes in epithelial stage V up to step 5 spermatids. A dose of 4 Gy of X-irradiation resulted in a transient increase of p21^(Cip1/WAF1) staining in these cells with a maximum at 6 hr post irradiation, despite the fact that the irradiation did not induce an increase in the number of apoptotic spermatocytes. When a dose of 0.3 Gy was given, no increase in p21^(Cip1/WAF1) staining was observed. Using the TUNEL technique, a 10-fold increase in apoptotic spermatogonia was found after a dose of 4 Gy. However, no staining for p21^(Cip1/WAF1) was observed in spermatogonia, suggesting that these cells do not undergo a p21^(Cip1/WAF1)-induced G1 arrest prior to DNA repair or apoptosis. These data imply that p21^(Cip1/WAF1) is a factor which could be important during the meiotic prophase in spermatocytes and repair mechanisms in these cells, but not in spermatogonial cell cycle delay or apoptosis induction. Mol. Reprod. Dev. 47:240–247, 1997. © 1997 Wiley-Liss, Inc.     

Mortality among the liquidators of the Chernobyl accident: dose dependences and groups of the potential risk

Dynamics of the mortality and the mortality radiation risks among male emergency workers of 1986-1987 years of entrance to the Chernobyl zone is analyzed. The average dose of external gamma-exposure for this cohort equals 128 mGy. The size of the cohort at the beginning of the follow-up in 1992 was 47820 persons. For the follow-up period 1992-2006 statistically significant radiation risks of death rates have been estimated: for the mortality from all causes, the excess relative risk per Gy (ERR/Gy) equals 0.42 with 95% confidence interval (95% CI) (0.14-0.72); for the mortality from solid cancers ERR/Gy = 0.74, 95% CI (0.03-1.76); and for the mortality from the circulatory system diseases ERR/Gy = 1.01, 95% CI (0.51-1.57). Based on these estimates the risk groups were ranked among all Russian emergency workers (160 thousand persons): the group of the potential radiation risk with doses more than 150 mGy (33488 persons) and the group of the high radiation risk with doses more than 240 mGy (6054 persons).     

Estimated yield of double-strand breaks from internal exposure to tritium

Internal exposure to tritium may result in DNA lesions. Of those, DNA double-strand breaks (DSBs) are believed to be important. However, experimental and computational data of DSBs induction by tritium are very limited. In this study, microdosimetric characteristics of uniformly distributed tritium were determined in dimensions of critical significance in DNA DSBs. Those characteristics were used to identify other particles comparable to tritium in terms of microscopic energy deposition. The yield of DSBs could be strongly dependent on biological systems and cellular environments. After reviewing theoretically predicted and experimentally determined DSB yields available in the literature for low-energy electrons and high-energy protons of comparable microdosimetric characteristics to tritium in the dimensions relevant to DSBs, it is estimated that the average DSB yields of 2.7 × 10(-11), 0.93 × 10(-11), 2.4 × 10(-11) and 1.6 × 10(-11) DSBs Gy(-1) Da(-1) could be reasonable estimates for tritium in plasmid DNAs, yeast cells, Chinese hamster V79 cells and human fibroblasts, respectively. If a biological system is not specified, the DSB yield from tritium exposure can be estimated as (2.3 ± 0.7) × 10(-11) DSBs Gy(-1) Da(-1), which is a simple average over experimentally determined yields of DSBs for low-energy electrons in various biological systems without considerations of variations caused by different techniques used and obvious differences among different biological systems where the DSB yield was measured.     

The recovery of humoral immunity after the long-term action of tritium oxide at different irradiation levels

Dynamics of recovery of humoral immunity of CBA mice was studied 1, 3, 6 and 12 months after termination of long-term exposure to tritium oxide at various levels of absorbed doses (3, 5 and 9 Gy) and dose rates (3.3, 4.9 and 9.2 cGy.day-1). A severer and more stable residual radiation damage was observed in the department of lymphocyte precursors. A considerable decrease in the content of antibody producers was due to the lymphoid tissue hypoplasia. There was a direct relationship between the immunodeficiency and dose rate and total absorbed dose of beta radiation.     

Mutation induction by tritiated water and effects of deuterium oxide in cultured mouse leukemia cells

Induction of mutation to 6-thioguanine resistance was studied in L5178Y mouse leukemia cells after exposure to low-dose-rate gamma rays or tritiated water at dose rates of approximately 0.025 to 0.4 Gy/hr for 20 hr in the presence or absence of 45% (v/v) deuterium oxide. The effect of acute gamma-ray exposure was also examined. A higher frequency of induced mutations was observed after tritium beta rays than after gamma rays, both at equivalent doses and cell survival. Deuterium oxide enhanced the mutation induced by gamma rays and tritium beta rays but did not affect the survival-mutation correlation of the two radiations.