FORMATION OF DIHYDRODIOLS BY THE CHEMICAL OR ENZYMIC OXIDATION OF 7-HYDROXYMETHYL-12-METHYLBENZ[A]ANTHRACENE AND THE POSSIBLE ROLE OF HYDROXYMETHYL DIHYDRODIOLS IN THE METABOLIC ACTIVATION OF 7,12-DIMETHYLBENZ[A]ANTHRACENE

The formation of dihydrodiols from 7-hydroxymethyl-12-methylbenz[a]anthracene by rat-liver microsomal fractions, by mouse skin in short-term organ culture and by chemical oxidation in an ascorbic acid/ferrous sulphate/ EDTA system has been studied using a combination of thin-layer chromatography and high pressure liquid chromatography. The 3,4, 8,9- and 10,11-dihydrodiols were formed in all three systems. The 5,6-dihydrodiol was formed in rat-liver microsomal fractions and in chemical oxidation but was not detected as a metabolite of [7-3H]hydroxymethyl-12-methylbenz[a]-anthracene when this compound was incubated with mouse skin in shortterm organ culture The possible role of hydroxymethyl dihydrodiols in the in vivo metabolic activation of 7,12-dimethylbenz[a] anthracene in mouse skin has been studied using Sephadex LH-20 column chromatography. The results show that the hydrocarbon-nucleic acid products formed following the treatment of mouse skin in vivo with [7,12-3H]dimethylbenz[a]anthracene are not the same as those that are formed following the treatment of mouse skin under the same conditions with either 7-hydroxymethyl-12-methylbenz [a]anthracene or 7-methyl-12-hydroxymethylbenz[a]anthracene. © 1979.