[Mutagenic action of the dimethyl ester of terephthalic acid on murine somatic cells in vivo]. / Mutagennoe deistvie dimetilovogo éfira tereftalevoi kisloty na somaticheskie kletki myshi in vivo.

Mutagenic activity of dimethyl terephthalate (DMtP) was evaluated using the bone marrow micronucleus test in mice. Clear clastogenic effect with the highest response in 24 h after a single i.p. injection was obtained at all concentrations used (0.2-1.0 mM/kg). The time-course for the micronuclei induced by DMtP was in agreement with the literature data on fast excretion of phthalates from mammal body. The dose-response curve for DMtP-induced micronuclei was linear in form with the logarithmic component. The emergence of the latter was related to the elevation of the chemical's concentration to the level at which DMtP starts to exert toxic influence on bone marrow erythropoietic function. The comparison of the effect induced by DMtP with that of methyl nitrosourea indicated that DMtP could not be considered as a strong mutagenic compound. Susceptibility of the micronucleus test was compared with that of Drosophila dominant lethal test in terms of the concentrations at which equal clastogenic effect was seen. This comparison made it possible to conclude that the micronucleus test in mice was able to respond to much lower phthalate concentrations, as compared with the test in Drosophila. The results provided the evidence of capacity of dimethyl terephthalate to cause alterations of genetical structures in both somatic and germinal cells of two highly organized species in vivo.

Mutagenic effects of dimethyl terephthalate on mouse somatic cells in vivo.

The mutagenic activity of dimethyl terephthalate (DMtP) was evaluated in the micronucleus test in mice. A clear clastogenic effect was obtained at all concentrations studied (0.2-1.0 mmole/kg body weight). The maximum number of micronuclei occurred 24 h after a single intraperitoneal (i.p.) injection. The time-course for the DMtP-induced micronuclei was in agreement with the available data on the rapid excretion of phthalates from the mammalian body. The dose-effect response was best described by a linear equation with a logarithmic component. The emergence of the latter term was related to the toxic effects of DMtP at higher concentrations on bone marrow erythropoietic function. A comparison of the effects induced by DMtP and by methyl nitrosourea indicated that DMtP cannot be considered a strong mutagenic compound. We have compared the sensitivity of the mouse micronucleus test and that of Drosophila dominant-lethal test by contrasting the effects obtained at similar exposure doses. This comparison leads to the conclusion that the micronucleus test is capable of responding to far lower phthalate concentrations than the Drosophila dominant-lethal mutation test. Our results testify to the ability of dimethyl terephthalate to cause genotoxic damages in vivo in both somatic and germinal cells of higher organisms. Thus, the chemical in question may be of potential genetic hazard to man.

[Characteristics of mutagenesis induced by nitrosomethylurea in a mammalian multilocus system in vitro]. / Osobennosti mutageneza, indutsiruemogo nitrozometilmochevinoi v mnogolokusnoi sisteme in vitro u mlekopitaiushchikh.

The mutagenic effect of short- and long-term MNU exposition causing alkylation and that combined with carbamoylation, correspondingly, at the four specific gene loci of the CHO-AT3-2 Chinese hamster line was studied. The increase both in MNU mutagenic effects and in the range of induced changes resulted from intensification of carbamoylating processes. True point mutations occurred mainly on alkylation. When carbamoylation is increased, the quantity and variety of mutations change towards accumulation of the number of other genetic lesions, for example, frameshift mutations and deletions.

[Mutagenic action of cadmium chloride in mammals]. / Izuchenie mutagennogo deistviia khloristogo kadmiia na mlekopitaiushchikh.

The mutagenic effect of cadmium chloride on somatic cells of F1 hybrid mice CBA X C57B1/6J in vivo and on an established line of CHO-ATZ-2 Chinese hamster cells in vitro has been studied. The induction of micronuclei has been demonstrated in mouse marrow cells as well as induction of point mutations at loci controlling the synthesis of hypoxanthine-phosphoribosyltransferase, thymidine kinase, adenine phosphoribosyltransferase and the resistance of Na+/K+ ATPase to ouabain in the cell line CHO-AT-2. A peak of mutagenic activity under the action of subtoxic doses of cadmium chloride has been revealed.

[Arsenic trioxide inhibition of the thiophosphamide induction of mutations in mouse germ and somatic cells]. / Ingibirovanie trioksidom mysh'iaka induktsii mutatsii tiofosfamidom v polovykh i somaticheskikh kletkakh myshi.

After single i. p. injection of arsenic trioxide, at the dosage range of 1/4 to 1/40 LD50 into hybrid mice (CBA X C57B1/6J)F1, no induction of dominant lethals in male germ cells was observed. However, it led to an increase in the number of micronuclei in the erythrocytes of bone marrow. Treatment with the effective dose of thioTEPA, causing an increase in the number of dominant lethals in male germ cells and in the number of micronuclei in the erythrocytes of bone marrow, followed by injection of arsenic trioxide, resulted in inhibition of the mutagenic activity of thioTEPA. This inhibition increased proportionally with the dose of arsenic trioxide.