Genetic effects in mice exposed to the 10-km area around the Chernobyl Atomic Energy Station

Mice (CBAxC57BL) F of both sexes were exposed within the 10 km zone of Chernobyl nuclear power station. Genetic damage of phone chronic effect of increased radiation in exposed adult mice and in the course of embryogenesis was studied. The total absorbed radiation doses in testes varied from 1.85 to 0.42 Gy in embryos and from 3.4 to 2.7 Gy in adult males. Increase of dominant lethal mutations (DLM) and abnormal sperm heads (ASH) was only observed right after the end of exposure of adult males. The yield of reciprocal translocations (RT) in these males was relatively low. Among the males exposed at the stage of early embryogenesis, 4 heterozygotes for RT were revealed. In other males of this group the RT yield was low.     

Bleomycin: female-specific dominant lethal effects in mice.

Limited comparative data in mice indicate that chemical mutagens that induce dominant lethal mutations in males are not necessarily effective in females, but those which are effective in females are generally equally or more effective in males. Recently, however, a few chemicals have been identified that are female-specific with respect to induction of dominant lethal mutations. The antitumor antibiotic adriamycin is among them. Another antitumor antibiotic, bleomycin was examined for its ability to induce dominant lethal mutations in the reproductive cells of male and female mice. No dominant lethal or cytotoxic effects were observed in males treated with bleomycin, even at a maximum tolerated dose. In females, on the other hand, a dose nearly 1/4 of that used in males induced not only a high level of dominant lethal mutations but also killed oocytes in certain stages of follicular development. The effectiveness of bleomycin in inducing dominant lethal mutations in mouse oocytes makes it a valuable tool for investigating whether gonadal transport, inherent differences in the configuration of chromatin in the germ cells of the two sexes or other factors are responsible for the differential susceptibility to bleomycin, which implies potential gender-specific genetic risk in cancer chemotherapy.     

Comparison of radiation-and chemically-induced dominant lethal mutations in male mice

Ionizing radiation-induced dominant lethal mutations in all spermatogenic stages. After irradiation of male mice with 200 R the yield of induced mutations in early spermatids was twice the yield in spermatozoa, late spermatids, and spermatocytes. After irradiation with 400 R or 800 R the spermatocytes were the most sensitive stage for the induction of dominant lethal mutations. The frequency of radiation-induced dominant lethal mutations in postspermatogonial stages was dose-dependent. The yield of dominant lethal mutations in spermatogonia was independent of the dose.     

Indraline Radioprotective Effect against Genetic Damage in Mice

The effect of indraline on frequency of dominant lethal mutations induced by radiation in germ cells, reciprocal translocations, and testicle weight of male mice. The level of protective effect against genetic damage varied depending on the radiation dose and spermatogenesis stage. The values of the defense coefficient ranged from 0.15 to 0.35.     

Heritable translocation study in male mice with trimethyl phosphate

Dominant lethal and heritable translocation studies were performed in male mice receiving a single intraperitoneal injection of trimethyl phosphate (TMP). The germ cell stage investigated was the spermatid. Methyl methanesulfonate (MMS) was used as a positive control in the latter study. A dominant lethal assay gave marked dose-dependent increases in early fetal deaths. Heritable translocations were detected at 1000 or 1500 mg of TMP/kg in F1 male progeny when screening for semi-sterility and cytogenetically analyzing the meiotic or mitotic chromosomes. Translocation induction was higher at the higher TMP dose (14.3%) than at the lower dose (5.3%) and the yield from the higher dose was similar to that induced by 50 mg of MMS/kg (11.0%). Most of the translocation carriers were semi-sterile or sterile. The data confirm conclusions from other dominant lethal studies showing TMP to be capable of causing chromosomal damage in mouse spermatids and show that certain types of damage result in heritable translocations.     

Comparative investigations with Trypaflavin in metaphase-II oocytes and in dominant lethal assay

Summary Pregnant C3H mice were orally treated with 50 mg Trypaflavin/kg on day 7, 11, 14, or 15 post conception. The embryos were thus treated in utero with the test compound. At the age of 10 weeks, the dominant lethal assay was performed with F₁ females. Dominant lethal mutations were induced only in those mice treated in utero on day 7 of the prenatal stage.Female C3H mice were chronically treated with Trypaflavin (50x2 mg/kg/day; dissolved in drinking water). These mice were caged with untreated males. The percentage of preimplantation egg loss and the yield of dead implants per female was increased.Female NMRI mice were chronically treated with Trypaflavin (50x2 mg/kg/day by stomach tube). In metaphases II of unfertilized oocytes, the yield of all observed aberration types (aneuploidies, gaps, satellite associations, breaks and fragments, deletions, and interchanges) was increased weakly.The investigation of metaphase-II chromosomes was supported by the EC Contract No. 175-77-1 ENV D.     

Influence of the MR (mutator) factor on X-ray-induced genetic damage

The genetical effects induced by MR, in the progeny of outcrossed MR-males, include very high frequencies of visible and lethal mutations and chromosome aberrations. The hypothesis is that MR causes breaks at specific sites in the DNA where, subsequently, insertion sequences become integrated. To examine whether there exists an interaction between breaks and radiation induced lesions, MRh12/Cy males were crossed to Berlin K females and the male progeny from this cross carrying the MR or Cy chromosome were irradiated. The frequencies of X-linked recessive lethals and II-III translocations were determined. Non-irradiated MR and non-MR (Cy) male progeny were used in concurrent controls. The results show that the frequencies of II-III translocations in the MR-containing males is not significantly higher than in the controls. However, with regard to the production of recessive lethal mutations a clear synergism between MRh12 and X-irradiation was observed.     

Genetic action of 131I and 125I on the germ cells of male mice

A study was made of the genetic effects of iodine radioactive isotopes in male germ cells of (CBA X C57Bl)F1 hybrid mice. After a single intraperitoneal administration of Na131I (1.48 to 740 kBq/g) or Na125I (148 to 7400 kBq/g) to males the occurrence of dominant lethal mutations (DLM), reciprocal translocations (RT), and abnormal sperm heads (ASH) was studied. The radioactive iodine isotopes induced DLM at the postmeiotic spermatogenesis stages only. After the effect of the isotopes, the frequency of RT increased insignificantly with dose. The frequency of ASH was only increased with the highest 131I dose. Relative biological effectiveness of 131I and 125I was less than 1 with a reference to the indices under study.     

Effects of Dose on the Induction of Dominant-Lethal Mutations and Heritable Translocations with Ethyl Methanesulfonate in Male Mice

Genetic damage by ethyl methanesulfonate (EMS) in male mice was measured at doses ranging from 50 to 300 mg/kg with dominant-lethal mutations and reciprocal translocations as endpoints. No appreciable increase in dominant-lethal mutations was detected following a dose of 100 mg/kg. Dominant lethals induced by EMS were convincingly detected only after a dose of 150 mg/kg, but in the translocation experiment an increase in the genetic effect was detectable at the 50 mg/kg dose. It is likely that dominant lethals had also been induced at the 50 and 100 mg/kg doses, but were not detected due to the relative insensitivity of the dominant..lethal procedure. Thus, for detection of low levels of EMS-induced chromosome breakage, translocations are a much more reliable endpoint than are dominant-lethal mutations. A procedure for large-scale screening of induced translocations is described.—The dominant-lethal dose-response curve, plotted on the basis of living embryos as a percentage of the control value, is clearly not linear as it is markedly concave downward. Similarly, the translocation dose-response curve showed a more rapid increase in the number of translocations with dose than would be expected on the basis of dose-square kinetics. It is clear for both of these endpoints that the effectiveness of EMS in inducing chromosome breakage is proportionately much lower at low doses.     

Reciprocal translocations in mice found in the vicinity of the Chernobyl nuclear power station

A study was made of the incidence of genetic damage to germ cells of male mice taken from or exposed within the thirty-kilometer zone of Chernobyl, the contaminated no-man's-land around the reactor that failed. At all contamination levels mouse spermatocytes exhibited reciprocal translocations, a relatively low frequency of which increased with increasing dose rate. Heterozygotes, with respect to reciprocal translocations (5%), were found among males exposed to enhanced radiation background as early embryos.     

The effect of cystamine on the outcome of dominant lethal mutations and reciprocal translocations in sex cells of mice subjected to gamma-irradiation in different doses]

Protective effect of cystamine (150 mg/kg) against genetic damages induced by gamma-irradiation in germ cells of male mice of CBA strain (at doses of 100, 300, 600 r) was studied. The application of cystamine decreased the frequency of dominant lethal mutations induced by radiation in sperms, spermatids and spermatocytes. The degree of the protective effect of cystamine depended on a radiation dose. The protective effect of cystamine was the highest at the radiation dose of 300 r. It was negligible at the radiation dose of 100 r and was completely absent at the dose of 600 r. Cystamine did not affect the rate of induced reciprocal translocations in the spermatogonia at all the radiation doses used.     

The mutagenic effect of different types of irradiation on the sex cells of male mice. VIII. Frequency of development of reciprocal translocations in the spermatogonia of mice subjected to chronic gamma-irradiation]

The frequency of reciprocal translocations in mice spermatogonia after the exposure to chronic gamma-irradiation at doses of 100, 200, 300, 600, 920 r, at the dose rate of 4,2 r/day was investigated. It was shown that the mutation frequency increased insignificantly with the increase of the radiation dose (y =0,8+0.0011x). The comparison of the data obtained with earlier results revealed no changes in the yield of translocations at the reduction of the dose rate from 10 r/day to 4,2 r/day. The investigation of the genetic radiosensitivity of mice spermatogonia after a chronic gamma-irradiation showed a tendency to increase in their radioresistance.     

Studies on the mutagenic effect of contraceptive drugs. I. Induction of dominant lethal mutations in female mice

30 adult virgin female mice (2 strains) received either high or low doses of Anovlar or Lyndiol oral contraceptives and were tested for induction of dominant lethal mutations. The pregnant mice were dissected on Day 14 of pregnancy and total implantations, early deaths, late deaths, and corpora lutea were counted in each pregnancy. A significant reduction in fertile mating (p .025) was found in 1 strain of those who received the high dose of Lyndiol (10 times that of the low dose, which is physiologically equivalent to the human dose). This dose also increased the number of dead implants in both strains which resulted in higher estimates of dominant lethal mutations. It is concluded that when Lyndiol and Anovlar were given at the physiological dose level to control ovulation in mice, the frequency of dominant lethal mutations was not increased above the control level.     

Mutagenic effect of different types of irradiation on the sex cells of male mice. IX. Duration of preservation of radiation-induced reciprocal translocations during the course of the reproductive period]

The rate of induction of reciprocal translocations by gamma-irradiation of mouse spermatogonia was studied by cytological examination of descendent spermatocytes. The CBA mice were given a total single acute dose of 300 r or 3 times per 300 r with 7 and 28 days intervals. The irradiated mice were killed within 3,7 and 12 month after the irradiation. The frequency of translocations in 3 and 7 month after the treatment was the same. A 25% decrease in the yield of reciprocal translocations was observed in 12 months after the irradiation. It suggests that the genetic risk from ionizing radiation remains high a year after the irradiation.     

Mutagenic effect of different types of irradiation on the sex cells of male mice. X. Frequency of recessive lethal mutations and reciprocal translocations in the spermatogonia of mice subjected to fractional gamma-irradiation]

The frequency of recessive lethal mutations and reciprocal translocations was investigated in spermatogonia of CBA male mice which were thrice gamma-irradiated at doses of 300 r with 28 days intervals. The rate of induced recessive lethals was estimated 1) by comparison of embryos survival between the irradiated and control groups in mating of the F1 males with their daughters, and 2) by estimation the frequency of males heterozygotes for recessive lethals in the first generation. In the first case the frequency of recessive lethals was 2,8 +/- 0,8-10(-4) per r per gamete (for the pre- and post-implantation death) and 1,6 +/- 0,1-10(-4) per r per gamete (for the pre- and post-implantation death) and 1,6 +/- 0,1-10(-4) per r per gamete in the second case. The frequency of heterozygotes for reciprocal translocations in the first generations of males was 3,1 +/- 0,9-10(-5) per r per gamete.     

Heritable translocation test on random-bred mice after prolonged triethylenemelamine treatment.

Heritable translocation and dominant lethal tests were conducted with random-bred Swiss albino male mice. The animals were provided drinking water containing triethylenemelamine (TEM) for 4 weeks, and were then mated for 3 successive weeks for analysis of dominant lethality and production of F1 progeny. Potential translocation carriers among F1 males were selected after two breedings and confirmed by cytogenetic analysis. Translocation heterozygotes were obtained in offspring of the TEM-treated groups, but not in the control groups. In F1 males produced from the first week of mating, the frequencies of translocations were 0, 1.78 6.2 and 10.0% for the control group and groups receiving TEM at 0.0125, 0.025 and 0.050 mg/kg/day, respectively, and in those produced from the third week of mating, the values were 0 and 2.1%, respectively, for the control group and the group receiving TEM at 0.050 mg/kg/day. F1 males from the second week of mating were not studied for the induction of heritable translocations. TEM-induced dominant lethality and heritable translocations were most prominent in the first week of mating after 4 weeks of treatment. In addition, heritable translocations appeared to be a more sensitive endpoint than dominant lethal mutations for the measurement of mutagenic effects of TEM.     

Evaluation of genetic consequences of 238Pu incorporation into mammals

The genetic effects of gonadal burdens of 238Pu after single injection were studied in male mice. The activity of plutonium was 7 to 1850 Bk/g. The average doses of accumulated alpha-particles in testis varied from 2 to 96 Gy.10(-2), the dose rate being 0.004 to 1 Gy.10(-2) per day. The genetic end points are: the dominant lethal mutation rate; the frequency of reciprocal translocations; the recessive lethal mutation rate and frequency of abnormal sperm head morphology. For all tests used, no linear dependence of the effect on the alpha-dose was observed. The RBE value of alpha-irradiation was 10-20 relative to chronic gamma-irradiation.     

Effects of 2.45 GHz microwaves on meiotic chromosomes of male CBA/CAY mice

Male CBA/CAY mice were exposed daily (6 days a week) for 30 minutes in an environmentally controlled waveguide to continuous 2.45 GHz microwave radiation for 2 weeks at average whole body absorbed dose rates of 0.05, 0.5, 10, and 20 mW/g. Shan exposed animals served as controls. Chain translocations were observed at diakinesis at metaphase I in microwave exposed animals. The yield of translocations increased with exposure, and varied nonlinearly with dose rate. An increase in incidence of univalents was seen after exposure at 10 and 20 mW/g. The findings are interpreted to indicate interference with normal spermatogenesis during the exposure period.     

Increment kinetics of recessive lethal mutations and dominant lethals in offspring of Drosophila melanogaster on storage of methyl-methanesulfonate-treated sperm in females

The frequencies of sex-linked recessive lethal mutations in F1 males after feeding adult male Drosophila melanogaster with 0.25 and 0.5 mM methyl methanesulfonate (MMS) orally for 24 h increased approximately linearly with storage of the treated spermatozoa in females, whereas the number of hits of dominant lethals in the sperm after feeding 0.3 and 0.5 mM MMS increased approximately with the square of the storage time. Chromosome losses and mosaics in F1 males also increased with the dose of MMS to males, but their yields were too low to be analyzed quantitatively, only indicating a slight increase of chromosome loses and a slight decrease of mosaics with the time of storage of sperm. Maternal non-disjunctions (or chromosome losses), detected in F1 males, decreased with the dose of MMS to spermatozoa and their yield decreased with the time of storage of sperm of both MMS-treated and the control groups. A unitary model is proposed to explain the effect of storage on the dominant lethals and recessive lethal mutations.     

Genetic effects of 131I in reproductive cells of male mice

A study was made of the frequencies of dominant lethal mutations (DLM) in pre- and post-meiotic germ cells, reciprocal translocations (RT) in spermatogonia and abnormal sperm heads (ASH) induced by a single intraperitoneal administration of Na131I with an activity of 1.48-740 kBq/g to male mice. The frequency of DLM was shown to increase only when postmeiotic cells were exposed to the radionuclide. The RT frequency increased insignificantly with increases in the dose of 131I. The ASH frequency increased only when maximal doses of 131I were administered. The relative biological efficiency (RBE) of 131I with reference to the indices under study is less than 1.