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Comparative Metabolism of 7,12-Dimethylbenz(a)anthracene in Liver and Mammary Tissue¹

Department of Breast Surgery and Endocrine Research Laboratory, Roswell Park Memorial Institute, Buffalo, New York 14203

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.

¹ This study was supported by Grants CA-04632-13 and CA-04632-14 from the National Cancer Institute, NIH, USPHS.

² Portions of this work are taken from a thesis submitted in fulfillment of the requirements for the M.A. degree in physiology at the State University of New York at Buffalo, Roswell Park Graduate Division, Buffalo, N. Y.

³ To whom requests for reprints should be addressed at Department of Breast Surgery, Roswell Park Memorial Institute, 666 Elm Street, Buffalo, N. Y. 14203.

Received 5/25/73. Accepted 8/24/73.