[Influence of selection on the sensitivity of laboratory mice to the cytogenetic effect oof thioTEPA]. / Vliianie otbora na chuvstvitel'nost' laboratornykh myshei k tsitogeneticheskomu éffektu tioTEF.

The influence of selection and inbreeding on the sensitivity of laboratory mice to cytogenetic effect of thioTEPA was studied. Selection was started among genetically heterogenous "synthetic" population. The sensitivity of mice was estimated by the frequency of bone marrow cells with chromosome damages in males 24 hours after the treatment with 5 mg/kg of thioTEPA dose intraperitoneally. As a result, genetic determination of sensitivity to the mutagen was demonstrated and the TPS strain was developed which was 3 to 4 times more sensitive than "normal" standard strains.

[Chromosome aberrations induced by cyclophosphamide in the meiotic cells of male mice]. / Khromosomnye aberratsii, indutsirovannye tsiklofosfamidom v meioticheskikh kletkakh samtsov myshei.

Cyclophosphamide was given intraperitoneally in doses of 40, 80 and 160 mg/kg to C57BL/6 male mice. Cytogenetic effect in spermatogonia of A and B types and in pachytene spermatocytes was studied by the frequencies of chromosomes recorded in cells at the stage of diakinesis MI meiosis. In some cells cyclophosphamide induced structural chromosomal aberrations, including translocations and the disturbances of normal bivalent formation. The dose of 80 mg/kg induced translocations in spermatocytes with frequency 0.6% and appearance of 3% of translocation carriers in F1 generation. Three males were heterozygotes by the translocation of the Robertsonian type.

[WR, a new strain of mice, highly sensitive to the cytogenetic effect of thiotepa]. / Novaia liniia myshei WR--vysokochuvstvitel'naia k tsitogeneticheskomu éffektu tiotéf.

Mice of the WR strain (genotype -aa, +WY) were selected for the appearance of black spots with normal pigmentation, presumably due to genetic recombination in the W gene region. The frequency of heterozigotes +WY with black spots was 25% in the 11th generation. The cytogenetic effect of thioTEPA (dose 5 mg/kg) was investigated in bone marrow cells of C57BL/10 NZW, 101/H and 129/Re mice. Mice of the WR strain were most sensitive to thioTEPA. It is suggested that the WR mice may be used as a sensitive object for the genetical screening of chemical compounds.

Effects of alkylating agents on lymphocytes from controls and from patients with Fanconi's anemia. Studies of sister chromatid exchanges, chromosome aberrations, and kinetics of cell division.

The frequency of sister chromatid exchanges (SCE) and chromosome aberrations and the dynamics of cell division in peripheral blood lymphocytes of four patients with Fanconi's anemia were studied after in vitro exposure to alkylating agents TEPA and mitomycin. SCE frequency was significantly increased even after very low doses of mutagens, while chromosome aberrations were significantly increased only after high doses (0.160 micrograms/ml mitomycin and 10(-5) M TEPA). The responses of Fanconi's anemia cells and control cells did not differ significantly. The increased frequency of both SCE and chromosome aberrations was accompanied by gradual delay of cell division, which was most conspicuous in cells from patients with Fanconi's anemia.

[Mutagenic effect of chemical compounds on laboratory mice]. / Issledovanie mutagennogo éffekta khimicheskikh soedinenii na laboratornykh myshakh.

Mutagenic effect of thioTEPA applied at a dose of 1.25 mg/kg was studied in late spermatids of C57BL/L male mice. The mutagen induced dominant lethal mutations in germ cells (39%) and symmetric translocations in 33.5% of F1 male offspring. The common frequency of sperms with chromosome mutations was 60%, that is ten times as much as the mutagenic effect in bone marrow cells. 39% of embryos at 3.5 days of development died or delayed their development at 2--22 blastomers stages. Structure chromosome aberrations were found in the cells of such embryos. The scheme of genetical screening of chemical compounds in laboratory mice, based on the data obtained early and in the present experiment, is proposed.

[Genetic control of mutability in laboratory mice. I. Genetic analysis of the sensitivity of mice of strains 101/H and C57BL/6 to the mutagenic effect of thio-TEPA]. / Geneticheskii kontrol' mutabil'nosti u laboratornykh myshei. Soobshchenie I. Geneticheskii analiz chuvstvitel'nosti myshei linii 101/H i C57BL/6 k mutagennomu éffektu tioTEF.

The distribution of male mice of the BC1 generation was analysed with respect to the frequency of chromosome aberrations in bone marrow cells induced by thio-TEPA. The BC1 descendants were derived from the F1 of the cross (C3H X 101) X 101 and the F1 of the cross (CBA X B6) X B6. With respect to mutability the BC1 descendants of both types could be divided into two classes. The average frequencies of the cells with chromosome aberrations in the BC1 descendants of the 101 line were in the two classes 33.4 and 64.2 percent respectively. The corresponding values for the two classes of the BC1 descendants of the B6 line were 24 percent and 33.2 percent respectively. These data suggest that each of the lines studied has one recessive mutator gene. Preliminary symbols are proposed: mut-1 for the gene of the line 101/H and mut-2 for the gene of the line B6. The gene mut-2 is linked with the gene a (nonagouti) (Vth linkage group, chromosome 2).

[Cytogenetic effect of mitomycin C and cytosine arabinoside on mice of different genotypes]. / Tsitogeneticheskii éffekt mitomitsina C i tsitozin-arabinozida u myshei raznogo genotipa

Cytogenetic effect of mitomycin C (MC) and cytosine arabinoside (CA) on bone marrow cells of male mice of the strains 101/HY, C57BL/6Y C,3H/SnY and of the (C3HX101) F1 hybrids was studied. The frequencies of cells with chromosome aberrations after the treatment with MC at a 5 mg/kg dose were 54,4%; 41,8%; 40,4% and 26,8% in 101H, B6, C3H/Sn mice and in the F1 hybrids (C3HX101) respectively. The frequencies of cells with chromosome aberrations after the treatment with CA at a 500 mg/kg dose were 25,2%; 17,8%; 10,8% and the 101/H, B6, C3H/Sn mice and in the F1 hybrids (C3HX101) respectively. Both mutagens induced the greatest number of chromosome aberrations in the 101/H strain and the smallest number in the F1 hybrid (C3HX101). A positive correlation was established between the levels of induced and spontaneous chromosome lesions.

[The mutagenic effect of thio-TEPA in laboratory mice. III. A comparison of the effect of different doses in the generative and somatic cells of male mice]. / Mutagennyi éffekt tioTEF u laboratornykh myshei. Soobshchenie III. Sravnenie éffekta raznykh doz v generativnykh i somaticheskikh kletkakh samtsov myshei

The solution of thio-TEPA was injected intraperitoneally to male mice of C57BL strain at doses of 5, 2.5; 0.32 and 0.16 mg/kg. The mutagenic effect of thio-TEPA in germ cells was investigated by means of the method of dominant lethals and compared to the cytogenetic effect in bone marrow cells. Late spermatids were the most sensitive to 5, 2.5 and 0.32 mg/kg doses. The frequency of dominant lethals induced by the 2.5 mg/kg dose in late spermatids is four times as high as that of bone marrow cells with chromosome anomalies. After the treatment with the 0.16 mg/kg dose only 1.4% gaps were recorded in bone marrow cells, while dominant lethal mutations were induced in 8--16% of spermatocytes. An assumption is made that the specific sensitivity of the stages of spermatogenesis to chemical mutagens depends not only on the characteristics of the mutagen, but on the dose used as well. The method of dominant lethals is more sensitive, than the cytogenetic analysis of chromosome lesions in bone marrow cells.

[The mutagenic effect of thioTEPA in laboratory mice. IV. The influence of genotype and sex on the frequency of induced chromosome aberrations in bone marrow cells]. / Mutagennyi éffekt tioTEF u laboratornykh myshei. Soobshchenia IV. Vliianie genotipa i pola na chastotu indutsirovannykh khromosomnykh aberratsii v kletkakh kostnogo mozga

In bone marrow cells of eleven genotypes of mice strain and sex variations in sensitivity to cytogenetic effect of thio-TEPA were studied. Strains 101/H, C57BL/6 and A/Sn were the more sensitive and F1 (CBAXC57BL/6) and F1 (C3HX101) were the more resistant to induction of chromosome damages. The rate of induced chromosome aberrations was correlated with the level of spontaneous chromosome damages in bone marrow cells (r=+/-0,893+/-0,02). From all strains males were more mutable than females. It is recommended to use C57BL/6 strain of mice male for genetic tests of chemicals by cytogenetic methods in vivo.

[The mutagenic effect of thioTEPA in laboratory mice. V. The influence of female genotype on the realization of dominant lethal mutations induced in male spermatids]. / Mutagennyi effekt tioTEF u laboratornykh myshei. Soobschenie V. Vliianie genotipa samok na reslizatsiiu dominantnykh letal'nykh mutatsii, indutsirovannykh v spermatidakh samtsov

Hybrid male mice (F1 males derived from the cross DBA/2 X AKR) were injected intraperitoneally with thio-TEPA at a 2 mg/kg dose. The mutagenic effect was determined from the frequency of dominant lethal mutations induced in spermatids of males. The malles were mated during the second and the third week after the injection to females of the strains C57BL/6, CBA/lac and to the F1 hybrid females derived from the cross CBA X C57BL/6 differing in the frequency of spontaneous and induced aberrations in bone marrow cells. In the course of investigation of pregnant C57BL/6 females, F1 (CBA X C57BL/6) and CBA/Lac females the frequency of dominant lethals induced in late spermatidis was established to be 63.4, 54.0and 37.9% respectively. The differences were interpreted as the evidence of different rates of recovery of a certain proportion of premutational lesions of the chromosomes of sperms in fertilized eggcells of female mice. No significant differences between the groups of females were observed in case of the treatment of early spermatids. It is established that the F1 hybrids derived from the cross DBA/2X XAKR are characterized by a high mutability.

Mutagenic effect of thioTEPA in laboratory mice. V. Influence of female genotype on realization of dominant lethal mutations induced in the spermatids of males. / Mutagennyi effekt tioTEF u laboratornykh myshei. Soobschenie V. Vliianie genotipa samok na realizatsiiu dominantnykh letal'nykh mutatsii, indutsirovannykh v spermatidakh samtsov

Hybrid male mice (F1 males derived from the cross DBA/2 x AKR) were injected intraperitoneally with thio-TEPA at a 2 mg/kg dose. The mutagenic effect was determined from the frequency of dominant lethal mutations induced in spermatids of males. The males were mated during the second and the third week after the injection to females of the strains C57BL/6, CBA/lac and to the F1 hybrid females derived from the cross CBA x C57BL/6 differing in the frequency of spontaneous and induced aberrations in bone marrow cells. In the course of investigation of pregnant C57BL/6 females F1 (CBA x C57BL/6) and CBA/Lac females the frequency of dominant lethals induced in late spermatids was established to be 63.4, 54.0 and 37.9% respectively. The differences were interpreted as the evidence of different rates of recovery of a certain proportion of premutational lesions of the chromosomes of pserms in fertilized egg cells of female mice. No significant differences between the groups of females were observed in case of the treatment of early spermatids. It is establihsed that the F1 hybrids derived from the cross DBA/2 x AKR are characterized by a high mutability.