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.     

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.     

Mutagenic action of cadmium on the sex cells of male mice

Possible mutagenic effect of cadmium chloride was studied by determining the frequency of dominant lethal mutations induced in germ cells of male mice. Water solution of CdCl2 was injected intraperitoneally to male mice at doses of 1.0, 2.0 and 4.0 mg/kg. The results obtained did not reveal any mutagenic effect of this compound. The dose of 4.0 mg/kg CdCl2 resulted in the death of spermatocytes and spermatogonia and the sterility of male mice. Cadmium chloride at a dose of 2.0 mg/kg did not affect the frequency of dominant lethal mutation induced by gamma-rays 60Co at a dose of 450 r in germ cells of male mice.     

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.     

Mutagenic effect of human adenovirus type I on the somatic and sex cells of male mice

Human adenovirus 1 was studied for its effect on the chromosomal apparatus both in bone marrow cells and male sex cells of mice. Chromosome aberrations were most early detected in spermatocytes of the 1st order mice infected with human adenovirus 1. In bone marrow cells of mice the highest level of chromosome aberrations was observed 30, 60, 90 days after the inoculation, which corresponds to a more frequent detection of the adenoviral antigen. The UV-irradiated-virus caused chromosome aberrations in the later periods after the inoculation which might be induced by the virus reactivation in a cell.     

Diagnostic irradiation of women during the reproductive period.

The date of onset of the last menstrual period should be given on radiographic requisitions for all women of reproductive age. Every effort should be made to avoid unnecessary irradiation of any woman who might be pregnant. Radiation damage in the first 2 weeks of pregnancy, however, should be "all or none", resulting in either a miscarriage or a normal child. Diagnostic radiology procedures are not indications for therapeutic abortion. Ultrasound has now replaced ionizing radiation in most examinations of the fetus and placenta. Pelvimetry should be done only when the decision to do a cesarean section hinges on precise knowledge of measurements of the bony pelvis. On the rare occasion when a radiograph of the fetus is necessary the woman should be prone for the examination. All such examinations are best ordered after consultation with a radiologist. Radiography of distant areas with the beam directed away from the woman''s abdomen can be done without concern at any stage of pregnancy.     

Dynamics of alpha-fetoprotein concentration in mice of different genotypes during the neonatal period]

A comparative assay of the alpha-fetoprotein (alpha-FP) level in mice of various genotypes (CBA, C3H, C57BL/Se/Sn, BALB/c, CC57W, AKR and nude--nu/nu) was conducted in the course of 3 weeks of postnatal period. The concentration of alpha-FP reached the following levels: the first day 2(-10)-2(-9); the 5th day 2(-8); the 8th day 2(-7); the 15th day 2(-4); on the 22nd day the level was zero. Nude mice which showed the alpha-FP concentration of 2(-2) on the 15th day were an exception. A conclusion was drawn that the alpha-FP synthesis was based not on the athymia of nude mice per se, but upon other unknown factors.     

Relation between the radioprotective effect of helium-neon laser radiation on bacterial cells and the time period between 2 types of irradiation

The effect of helium-neon laser radiation (lambda = 633 nm) given to E. coli K-12 cells of various genotypes 4 h following X- or alpha-irradiation was shown to increase the number of viable cells. The irreversible ingradient of a radiation injury to cells remained invariable during the first 60 min after irradiation its values being minimal.     

The effect of cadmium on the survivability of colony-forming hematopoietic cells in mice exposed to x-ray irradiation]

It has been reported elsewhere that in addition to enhancing the expression of metallothionein genes, the previous injection of cadmium salts into sublethally X-irradiated mice increases by 10 times the number of endogenous spleen colonies. To understand the mechanism of the strong radioprotective cadmium effect donors and recipients were treated separately. It is shown that the survival of exogenous bone marrow colony-forming cells in lethally irradiated recipient remains at the control level independently of the donor cadmium treatment, whereas the injection of cadmium nitrate to recipient mice leads to the stimulation of colony formation by 1.7-1.8 times. The data allow to conclude that the cadmium effect on the survival of colony-forming hemopoietic murine cells after X-irradiation is not mediated by the enhanced expression of metallothionein genes.     

Long-term effects of irradiation before adulthood on reproductive function in the male rhesus monkey.

Today, many patients, who are often young, undergo total body irradiation (TBI) followed by bone marrow transplantation. This procedure can have serious consequences for fertility, but the long-term intratesticular effects of this treatment in primates have not yet been studied. Testes and epididymides of rhesus monkeys that received doses of 4-8.5 Gy of TBI at 2-4 yr of age were studied 3-8 yr after irradiation. In all irradiated monkeys, at least some seminiferous tubule cross-sections lacked germ cells, indicating extensive stem cell killing that was not completely repaired by enhanced stem cell renewal, even after many years. Testes totally devoid of germ cells were only found in monkeys receiving doses of 8 Gy or higher and in both monkeys that received two fractions of 6 Gy each. By correlating the percentage of repopulated tubules (repopulation index) with testicular weight, it could be deduced that considerable numbers of proliferating immature Sertoli cells were killed by the irradiation. Because of their finite period of proliferation, Sertoli cell numbers did not recover, and potential adult testis size decreased from approximately 23 to 13 g. Most testes showed some dilated seminiferous tubules, indicating obstructed flow of the tubular fluid at some time after irradiation. Also, in 8 of the 29 irradiated monkeys, aberrant, densely packed Sertoli cells were found. The irradiation did not induce stable chromosomal translocations in spermatogonial stem cells. No apparent changes were seen in the epididymides of the irradiated monkeys, and the size of the epididymis adjusted itself to the size of the testis. In the irradiated monkeys, testosterone and estradiol levels were normal, whereas FSH levels were higher and inhibin levels lower when testicular weight and spermatogenic repopulation were low. It is concluded that irradiation before adulthood has considerable long-term effects on the testis. Potential testis size is reduced, repopulation of the seminiferous epithelium is generally not complete, and aberrant Sertoli cells and dilated tubules are formed. The latter two phenomena may have further consequences at still longer intervals after irradiation.     

The effect of phosphoenolpyruvate on the course of the acute period in experimental myocardial infarct]

It was found in the experiments on dogs, that phosphoenolpyruvate decreased the level of regional metabolic acidosis, stabilized energy metabolism, cardiohemodynamics and enhanced the blood supply of the ischemic myocardium. Anti-ischemic effect of the phosphoenolpyruvate was more significant in comparison with fructose-1,6-diphosphate in isomolar doses.     

The cytoradiography of the DNA and proteins in different types pf cells after the irradiation of rats with decimeter waves]

Microwave (2450 MHz, 1 mW/cm2, continuous regime) influence on DNA and protein synthesis in bone marrow, testes and liver cells of Fisher-line rats at early stage of formation of defence-adaptation reactions was studied. Cytoradiographic analysis of tissue smears and prints using 3H-thimidine and 35S-methionine was made. Type of reaction to microwave irradiation depends on ploidy, rate of differentiation and functional activity of cells.     

Effects of alcoholic intoxication in the antenatal period on the development of male germ cells]

During 1-20 days of pregnancy rats were given 20% alcohol orally in a dose 0.4 mg/kg bw. This led to a significant increase in the nuclear volume of germ cells in male 19-day embryos. A karyological analysis of 2-month offspring germ cell generations at stage VII of seminiferous epithelium cycle revealed a reliable decrease in the number of spermatids on step 7 of development after introduction of antenatal alcohol. The increased proportion of spermatocytes with meiotic chromosomes pathological behaviour due to alcohol was determined by the proposed quantitative analysis of meiotic divisions.     

Genetic injury in hybrid male mice exposed to low doses of 60Co gamma-rays or fission neutrons. III. Frequencies of abnormal sperm and reciprocal translocations measured during and following long-term weekly exposures

Male B6CF1 mice were exposed to either fission neutrons or 60Co gamma-rays at once-weekly doses approaching occupational levels for periods up to 60 weeks. Both during and after the irradiation sequence, the mice were screened to determine the incidence of abnormal epididymal sperm and of reciprocal chromosome translocations in metaphase spermatocytes. Abnormal sperm frequencies equilibrated with dose/week by 10 weeks and also showed an additive nonlinear seasonal increment. The relative biological effectiveness (RBE) for these damages is 12 +/- 1. After exposures ended, sperm frequencies in gamma-irradiated mice quickly returned to near-normal levels. Neutron-irradiated males showed a significantly elevated level of abnormalities for approximately 30 weeks--a paradoxical finding--as no clear evidence of cumulative injury was seen during exposure. When assayed at 10 and 25 weeks of exposure but not later, translocation frequencies demonstrated an increment, significant in the neutron series, attributed to irradiated spermatocytes. Dose-response analysis with cumulative dose up to the 60-week maximum gave an RBE of 45 +/- 10. Post exposure, the incidence of translocations subsided slightly, but the RBE remained above 30.     

The effect of sampling time on radiation-induced translocation yield in spermatogonial stem cells of male mice, differing in chromosomal constitution and sexual activity

We have investigated the frequency of reciprocal translocations in the first differentiating spermatogonia entering the first meiotic division after 2 x 2.5 Gy X-rays, given 24 h apart, as well as the development of this parameter in later stem-cell generations by studying multivalent configurations at the first meiotic division. Diakinesis-metaphase I cells were found for the first time between 30 and 40 days after irradiation. Subsequently, meiotic stages were sampled at 120, 180 and 280 days post irradiation. From day 40 post irradiation on, half of the males were allowed to impregnate females which enabled us to estimate the length of the post-irradiation sterile period, the development of litter size and the possible effect of sexual activity on the development of reciprocal translocation-containing stem cells. Half of the males were karyologically normal, the other half were homozygous for a reciprocal translocation (T/T) that affects testis weight and about halves sperm production. Irrespective of male karyotype, the first meiocytes had an induced translocation frequency of 9.00 +/- 2.56% (n = 8 males), followed by frequencies of 20.70 +/- 4.87% (n = 15) at 180 days and 20.20 +/- 4.30% (n = 20) at 280 days (males with and without mating behavior showing no difference). At 120 days post irradiation, +/+ males had a frequency of 14.59 +/- 2.97% irrespective of sexual activity. T/T males (120 days post irradiation) that had mated showed a frequency of 18.63 +/- 0.85% (n = 4) compared with 13.64 +/- 2.36% (n = 7) for those that had not. The observed rise of multivalent-carrying spermatocytes in time was highly significant. Notwithstanding the differences in testis weight and epididymal sperm count between the karyotypes, fertile matings occurred on average 72 days after irradiation, though with relatively wide margins. For the T/T karyotype, the first litter was statistically smaller than the subsequent litters. At 78 days post irradiation, testis weights were back in the subnormal range for both karyotypes and hardly improved in time. Restoration of fertility thus coincided with the period just prior to the return to subnormal testis weights. The first diakinesis-metaphase I cells precede those that are numerous enough to accomplish 'return to fertility' by about 2 weeks. Thus differentiation of stem-cell spermatogonia already follows a few days after irradiation. A pattern of spermatogonial cell divisions compatible with 'return to fertility' is only established some 2 weeks later.