Glutathione Conjugates as Metabolites of Benz[a]anthracene

Abstract

1. [³H]Benz[a]anthracene is converted into water-soluble metabolites by microsomal plus soluble fractions of rat-liver in the presence of NADPH and glutathione. Chromatography on Sephadex G25 gave four radioactive peaks; the first contained hydrocarbon or hydrocarbon derivatives bound to soluble protein while the other three peaks contained glutathione conjugates of hydrocarbon metabolites.

2. Conjugates formed when either of the benz[a]anthracene metabolites, 5,6-dihydro-5,6-dihydroxybenz[a]anthracene or 8,9-dihydro-8,9-dihydroxybenz-[a]anthracene, were similarly incubated were probably S-(5,6,8,9-tetrahydro-5, 6, 9-trihydroxybenz[a]anthracen-8-yl)glutathione and S-(5,6,8,9-tetrahydro-6,8, 9-trihydroxybenz[a]anthracen-5-yl)glutathione respectively. The corresponding peak obtained in the metabolism of benz[a]anthracene probably contains a mixture of these two isomers.

3. The third peak contained the conjugate, S-(5,6-dihydro-6-hydroxybenz-[a]anthracen-5-yl)glutathione, also formed by the conjugation of the ‘K-region’ epoxide of benz[a]anthracene with glutathione. This was not formed in the metabolism of the dihydrodiols.

4. The fourth peak contained a new type of conjugate that is probably S- (8,9,10,11 - tetrahydro - 8,9,10-trihydroxybenz[a]anthracen-11 - yl) glutathione. This conjugate is chromatographically similar to a product obtained from incubation of the 8,9-dihydrodiol, and is probably formed by microsomal oxidation of the 10,11-bond of the dihydrodiol, followed by conjugation of the resulting diol-epoxide with glutathione.