Mutagenicity of benzo[a]pyrene 7,8-dihydrodiol and 7,12-dimethylbenz[a]anthracene 3,4-dihydrodiol in S. typhimurium mediated by microsomes from rat liver and mouse skin |
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Authors: | A M Camus W G Pyerin P L Grover P Sims C Malaveille H Bartsch |
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Affiliation: | 1. International Agency for Research on Cancer, 150 cours Albert-Thomas, 69372 Lyon, Cedex 2 France;2. German Cancer Research Centre, Institute of Experimental Pathology, Heidelberg F.R.G.;3. Chester Beatty Research Institute, Institute of Cancer Research: Royal Cancer Hospital, Fulham Road, London SW3 6JB United Kingdom |
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Abstract: | The mutagenic activities of trans-7,8-dihydro-7,8-dihydroxybenzo[a]-pyrene (BP 7,8-diol) and of trans-3,4-dihydroxy-7,12-dimethylbenz[a]-anthracene (DMBA 3,4-diol) towards S. typhimurium TA100 were measured in assays that were carried out on a micro-scale in liquid medium in the presence of microsomal fractions prepared from mouse skin or rat liver. In the presence of an NADPH-generating system, microsomal enzymes converted both diols into mutagens that were probably the respective 'bay-region' diol-epoxides. The rate of the enzyme-catalysed conversion of the BP 7,8-diol into mutagens by microsomal preparations from mouse epidermis was similar to that occurring with microsomes from rat liver. Pretreatment of mice by the topical application of benz[a]anthracene (BA) or 7,12-dimethylbenz[a]-anthracene (DMBA) increased the mutagenic activity of BP 7,8-diol mediated by mouse skin microsomal preparations by 2-fold and this was paralleled by a 4-fold increase in epidermal aryl hydrocarbon (benzo[a]pyrene) hydroxylase (AHH) activity. The results are discussed in relation to the high susceptibility of mouse skin to polycyclic aromatic hydrocarbon (PAH) carcinogenesis. |
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Keywords: | AHH BA BP BP 7,8-diol DMBA DMBA 3,4-diol PAH polycyclic aromatic hydrocarbon |
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