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 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.
D000818:Animals; D001711:Biotransformation; D002911:Chrysenes / Q000378:metabolism*; D005453:Fluorescence; D005978:Glutathione / Q000378:metabolism*; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism; D010616:Phenanthrenes / Q000378:metabolism*; D051381:Rats
D002911:Chrysenes; D010616:Phenanthrenes; C050404:9-hydroxychrysene-1,2-diol-3,4-oxide; C021977:chrysene,2-diol-3,4-epoxide-1; D005978:Glutathione