Role of the carbamoylation reaction in the biological activity of methyl nitrosourea.

Study of the mutagenic action of methyl nitrosourea (MNU) on the CHO-AT3-2 Chinese hamster cell at 2 regimes of cell treatment (a short-term regime and prolonged 1-h treatment) revealed that increase in the duration of treatment enhanced both cell lethality and clastogenic and mutagenic effects at the TK locus and did not influence the mutation frequency at the OUAr locus. On the basis of kinetic considerations it can be concluded that the base-pair substitution-type mutants (e.g.

Increased antimutagenic activity of simple substituted phenols mixed with the hindered phenolic antioxidant dibunol.

The micronucleus test using mouse bone-marrow polychromatic erythrocytes was used to study the extent to which benzo[a]pyrene (BP) mutagenicity was inhibited by mixtures of simple phenols (resorcinol and pyrogallol) with and without the complex hindered-phenol antioxidant dibunol (2,6-di-tert-butyl-4-methylphenol). Mixtures of these phenolic compounds inhibited BP mutagenicity more effectively than did the individual constituents. One can assume that the simple phenols regenerated in the presence of dibunol from the tissue-oxidized forms increase the formation of detoxified or less mutagenic metabolites of BP.

Mutagenic effects of thiram in mammalian somatic cells.

The dimethylthiocarbamate fungicide thiram has been found to be a potent and direct inducer of point mutations at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in Chinese hamster cells in vitro. It also increased the incidence of micronuclei in polychromatic erythrocytes in the bone marrow of mice given a single ip dose of 100 mg/kg. Both the in vitro and the in vivo mutagenic responses were observed with doses of thiram that were cytotoxic.

Inhibition of the mutagenicity of benzo[a]pyrene in the V79/HGPRT system by bioantioxidants.

In the presence of metabolic activation (S9 microsomal fraction of mouse-liver homogenate) the mutagenicity of benzo[a]pyrene (BP) in Chinese hamster V79 cells was inhibited by the phenolic bioantioxidants (BA) Dibunol (2,6-di-tert-butyl-4-methylphenol-D) and 5-methylresorcine(5-MR). The mixture BP + D and BP + 5-MR at molar ratios of 1:1 and 1:85 respectively showed no mutagenic activity compared to the control. One can assume that D and 5-MR inhibited BP-induced mutagenesis by binding the free radicals of BP metabolites with the formation of less active phenolic derivatives and also by linkage with cytochrome P-450, which prevents further metabolic activation of BP.