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

Chem Biol Interact. 1980 Nov;32(3):257-65. doi: 10.1016/0009-2797(80)90093-9.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene / analogs & derivatives
  • 9,10-Dimethyl-1,2-benzanthracene / pharmacology*
  • Animals
  • Aryl Hydrocarbon Hydroxylases / analysis
  • Benz(a)Anthracenes / pharmacology*
  • Benzopyrenes
  • Dihydroxydihydrobenzopyrenes*
  • Dose-Response Relationship, Drug
  • Female
  • Male
  • Mice
  • Microsomes / metabolism*
  • Microsomes, Liver / metabolism*
  • Mutagenicity Tests
  • Rats
  • Salmonella typhimurium / drug effects*
  • Skin / metabolism*

Substances

  • Benz(a)Anthracenes
  • Benzopyrenes
  • Dihydroxydihydrobenzopyrenes
  • benzo(a)pyrene 7,8-dihydrodiol
  • 9,10-Dimethyl-1,2-benzanthracene
  • 7,12-dimethylbenz(a)anthracene-3,4-dihydrodiol
  • Aryl Hydrocarbon Hydroxylases