Metabolism of the bay-region diol-epoxide of chrysene to a triol-epoxide and the enzyme-catalysed conjugation of these epoxides with glutathione

Carcinogenesis. 1986 Dec;7(12):2095-8. doi: 10.1093/carcin/7.12.2095.

Abstract

Metabolic activation of chrysene in mouse skin appears to involve r-1,t-2-dihydroxy-t-3,4-oxy-1,2,3,4-tetrahydrochrysene (anti-chrysene-1,2-diol 3,4-oxide) and 9-hydroxy-r-1,t-2-dihydroxy-t-3,4-oxy-1,2,3,4-tetrahydrochrysene (anti-9-OH-chrysene-1,2-diol 3,4-oxide). The enzyme-catalysed conjugation of these epoxides with [35S]glutathione has been studied in experiments in which the glutathione conjugates were separated by h.p.l.c. and examined by fluorescence spectrophotometry. Both anti-chrysene-1,2-diol 3,4-oxide and anti-9-OH-chrysene-1,2-diol 3,4-oxide formed conjugates nonenzymically and both were shown to be substrates for rat liver glutathione transferases. When anti-chrysene-1,2-diol 3,4-oxide was incubated with [35S]glutathione and a rat liver microsomal metabolizing system, glutathione conjugates with h.p.l.c. and fluorescence spectral characteristics identical to those of conjugates formed from both anti-chrysene-1,2-diol 3,4-oxide and anti-9-OH-chrysene-1,2-diol 3,4-oxide were detected. This finding provides evidence that anti-chrysene-1,2-diol 3,4-oxide can be further metabolized to the triol-epoxide, anti-9-OH-chrysene-1,2-diol 3,4-oxide by rat liver microsomal systems.

Publication types

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

MeSH terms

  • Animals
  • Biotransformation
  • Chrysenes / metabolism*
  • Fluorescence
  • Glutathione / metabolism*
  • In Vitro Techniques
  • Microsomes, Liver / metabolism
  • Phenanthrenes / metabolism*
  • Rats

Substances

  • Chrysenes
  • Phenanthrenes
  • 9-hydroxychrysene-1,2-diol-3,4-oxide
  • chrysene,2-diol-3,4-epoxide-1
  • Glutathione