Search

On the 12th day of pregnancy CBA, 101/H and AKR mice were given thiophosphamide in a dose of 5 mg/kg bw, and were sacrificed on the 19th day of pregnancy. The action of thiophosphamide on embryonal ovaries and testes was studied by assaying for the population of oocytes and relative number of the different stages of meiotic prophase I; index of the degeneration germ cells; for the population of prospermatogonies and their degeneration; morphometric study of nucleus of nucleolus of prospermatogonies. A significant decrease of germ cells was found in male and female embryos on the 19th day of pregnancy after thiophosphamide injection. Interspecific differences were found as regards the number of germ cells and their proportion in health as well as in response to a single antenatal injection of thiophosphamide.

Spontaneous and mitomycin-C-induced chromosomal aberration level was studied in bone marrow cells of mice F1 (NZBXNZW), an experimental model of systemic lupus erythematosus and in C57BL/6J mice. The chromosome instability level is found to correspond to the degree of the autoimmune process: F1 (NZBXNZW) mice with the highest titer of autoantibodies to DNA has higher chromosomal mutability.

On crossing of thiophosphamide treated CBA males to untreated A/He, C57BL/6, C57BL/Mib and fidget females the lowest output of dominant lethal mutations was found in progeny of C57BL/Mib females. It is suggested that the ceparation of premutational lesions is most effective in egg cells of this strain.

It has been shown that 101/H mice differ from CBA mice by a higher sensitivity to the teratogenic action of the alkylating agent thiophosphamide.

Studies of 5-day mice F1 (CBA X C57Bl) demonstrated that an exposure of animals to acute hypoxia (5% O2--95% N2) during their irradiation produced a different effect on the spleen and the growing cerebellar cortex. In these circumstances lesions of well oxygenated spleen tissues were noticeably reduced, whereas cerebellar cortex cells characterized by a low oxygen tension and a high tolerance to anoxia remained essentially unprotected. The findings are discussed in the light of adaptation concepts postulating that oxygen tension in cells is regulated, depending on the level of its uptake which in turn is determined by the relative oxygen content in the surrounding medium.

Chromosomal aberrations were studied in cells of embryonic liver and bone marrow of A/He and C57BL/6 mice following mutagenic treatment by the alkylating agent thiophosphamide in g1-S periods of the cell cycle. Higher sensitivity of chromosomes to aberration induction was found in A/He mice.

Chromosome aberrations were studied in cells of embryo liver of 101/H and CBA mice following mutagenic treatment with the alkylating agent--thiophosphamide. Higher sensitivity of chromosomes to aberration induction was found in 101/H mice. After crossing thiophosphamide treated 101/H and CBA males to untreated 101/H and CBA females, the lowest output of dominant lethal mutations was found in the progeny of 101/H females. It is suggested that the 101/H mice are a possible model of inherited diseases with chromosomal instability.

The same damages were found to occur in hepatocyte DNA from old mice of different strains by means of sedimentation in alkaline sucrose concentration gradient. At the same time, the number of hepatocytes with aberrant chromosomes is strongly different in these strains. From these data an assumption is made that some other damages being accumulated with aging are responsible for chromosome aberrations except for single-strand DNA breaks. The number of single-strand breaks registered in hepatocyte DNA of the old animals under gamma-irradiation is two-three times more than that of the young animals, though the rates of repair of the induced single-strand breaks in DNA are the same for mice of different age and strains.

Sensitivity of bone marrow cell chromosomes to alkylating agent thiophosphamide and to gamma-irradiation has been studied in the course of ageing in 101/H, A/He, CBA, BALB/c and C57BL/6 mice. The effects of both the kinds of mutagenic treatment and of the genotype of the animals on the age-dependent changes in sensitivity of bone marrow cell chromosomes were found. Following gamma-irradiation under our experimental conditions, no variation in the output of chromosomal aberrations was observed between the strains studied. Following thiophosphamide treatment, aged mice of strains 101/H, A/He and CBA showed an increased chromosome instability as compared to young ones. In C57BL/6 mice the level of induced chromosome aberrations was found to be age-independent. Following thiophosphamide treatment, cells with multiple chromosome lesions were found in the bone marrow. The higher instability of aged animals in some strains was mainly due to a sharp increase in the number of such cells. In the intact mice of all the strains studied no age-dependent increase in the number of cells showing structural chromosome aberrations was observed, while accumulation of aneuploid cells varied with genotype.