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

Metabolic activation of chrysene in mouse skin appears to involver-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 epoxideswith ³⁵S]glutathione has been studied in experiments in whichthe glutathione conjugates were separated by h.p.l.c. and examinedby fluorescence spectrophotometry. Both anti-chrysene-1, 2-diol3, 4-oxide and anti-9-OH-chrysene-1, 2-diol 3, 4-oxide formedconjugates nonenzymically and both were shown to be substratesfor rat liver glutathione transferases. When anti-chrysene-1,2-diol 3, 4-oxide was incubated with ³⁵S]glutathione and arat liver microsomal metabolizing system, glutathione conjugateswith h.p.l.c. and fluorescence spectral characteristics identicalto those of conjugates formed from both anti-chrysene-1, 2-diol3,4-oxide and anti-9-OH-chrysene-1, 2-diol 3, 4-oxide were detected.This finding provides evidence that anti-chrysene-1, 2-diol3, 4-oxide can be further metabolized to the triolepoxide, anti-9-OH-chrysene-1,2-diol 3, 4-oxide by rat liver microsomal systems.