Metabolism and urinary excretion of mutagenic metabolites of benzo[a]pyrene in C57 and DBA mice strains

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Abstract
Groups of C57Bl/6 (B6) mice (responsive) and DBA/2 (D2) (non-responsive) mice received an i.p. dose of benzo[a]pyrene (BP) (100 mg/kg body weight) with or without pretreatment with or without pretreatment with β-naphthoflavone (BNF), an inducer of monooxygenases. The amount of mutagenic BP metabolites in the urine was determined by the Salmonella /microsome assay (strain TA100) and excretion of BP metabolites was quantifled by h.p.l.c. After inducer treatment, the responsive mice excreted more mutagens and total oxidized BP metabolites in the urine than did the non-responsive strain. The ratio of BP diols:total oxidized metabolites was 0.42 in B6 mice and 0.72 in D2 mice and was not affected by inducer treatment. After a dose of [ 14 C]BP, radioactivity was measured in the faeces for up to 7 days. The half-life of [ 14 C]BP in the non-responsive D2 mice was about twice that in the responsive B6 mice. Our results agree with a previously proposed model of the risk factors for toxic effects and/or the development of tumours after exposure to polycyclic aromatic hydrocarbons in responsive and nonresponsive mouse strains.