Comparative metabolism of 7,12-dimethylbenz(a)anthracene in liver and mammary tissue.

Abstract

The metabolism of 7,12-dimethylbenz(a)anthracene to hydroxymethyl derivatives differs in hepatic and mammary tissue homogenates. Countercurrent distribution and carrier recrystallization have been shown to be effective additional tools in the identification of 7-hydroxymethyl-12-methylbenz(a)anthracene, 12-hydroxymethyl-7-methylbenz(a)anthracene, and 7,12-dihydroxymethylbenz(a)anthracene. In the hepatic tissue, 7,12-dimethylbenz(a)anthracene is transformed into all three of these metabolites whereas the mammary gland formed only the monohydroxy compounds. Pretreatment of rats with 3-methylcholanthrene induces a marked increase in 7,12-dimethylbenz(a)anthracene-metabolizing enzymes in the liver causing further conversion of the 7-hydroxymethyl-12-methylbenz(a)anthracene, 12-hydroxymethyl-7-methylbenz(a)anthracene, and 7,12-dihydroxy-7,12-dimethylbenz(a)anthracene to more polar components. In contrast, mammary gland caused a diminution but still detectable level of the carcinogenic 7-hydroxymethyl-12-methylbenz(a)anthracene and a noticeable increase in the conversion to 12-hydroxymethyl-7-methylbenz(a)anthracene. The data illustrate, for the first time, the ability of the mammary tissue to metabolize 7,12-dimethylbenz(a)anthracene.