Estimation of genetic risks of alkylating agents. VI. Exposure of mice and bacteria to methyl bromide.
Methyl bromide was studied in a forward mutation system of E. coli to evaluate the relationship between dose and mutagenic response. The compound had a high toxicity and a low mutagenic efficiency, as expected from the high s value. The mutagenic effectiveness was estimated to be 1 mutation per 10(8) surviving bacteria per mM . h, in reasonable agreement with expectation from reaction kinetic data. To study the possibilities of using hemoglobin alkylation for an estimation of DNA alkylation in vivo, mice were treated with 14C-labeled methyl bromide. The degree of alkylation of DNA, determined in liver and spleen, was considerably lower than expected (200 and 20 times, respectively) from the degree of alkylation of hemoglobin and from the relative reactivities of DNA and hemoglobin towards methyl bromide in vitro. when hemoglobin alkylation is used for quantitative risk estimations, a correction factor has to be applied by taking into account the difference between the dose in red blood cells and the dose in the compartments of DNA.
D000478:Alkylation; D000818:Animals; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000235:genetics; D006454:Hemoglobins / Q000378:metabolism; D006842:Hydrocarbons, Brominated / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens; D013154:Spleen / Q000378:metabolism
D006454:Hemoglobins; D006842:Hydrocarbons, Brominated; D009153:Mutagens; D004247:DNA; C005218:methyl bromide