The Preparation of 7-Hydroxymethylbenz[a]anthracene 5,6-Oxide and its Metabolism by Rat-liver Preparations

Abstract

1. The syntheses and properties of 7-acetoxymethylbenz[a]anthracene 5,6-oxide, 7-hydroxymethylbenz[a]anthracene 5,6-oxide and trans-5,6-dihydro-5,6-dihydroxy-7-hydroxymethylbenz[a]anthracene are described. 2. 7-Hydroxymethylbenz[a]anthracene 5,6-oxide was converted by rat-liver microsomal preparations and homogenates into trans-5,6-dihydro-5,6-dihydroxy-7-hydroxymethylbenz[a]anthracene and by rat-liver soluble fraction and glutathione, or by rat-liver homogenates, into a glutathione conjugate. Small amounts of 5-hydroxy-7-hydroxymethylbenz[a]anthracene were sometimes formed in these incubations, probably by a non-enzymic reaction. 3. 7-Hydroxymethylbenz[a]anthracene was metabolized by rat liver microsomes into a number of products including the trans-5,6-dihydrodiol. This product was not detected when the hydroxymethyl derivative was incubated with rat liver homogenate. 4. 7-Hydroxymethylbenz[a]anthracene 5,6-oxide was less efficient in alkylating 4-(p-nitrobenzyl)pyridine than 7-methylbenz[a]anthracene 5,6-oxide.