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Metabolism of 7,12-Dimethylbenz(a)anthracene by Macrophages and Uptake of Macrophage-derived Metabolites by Respiratory Tissues in Vitro¹

Chemical Carcinogenesis Program, Frederick Cancer Research Center, Frederick, Maryland 21701

Cultured mouse macrophages and tracheal and lung tissue each produced the same ethyl acetate-soluble derivatives of 7,12-dimethylbenz(a)anthracene (DMBA). The derivatives produced in the different cultures were indistinguishable by thin-layer chromatography and by high-pressure liquid chromatography but differed in their relative proportions. The greatest difference was seen between lungs and macrophages. The predominant metabolite produced by lungs was 8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenz(a)anthracene, while macrophages produced equal quantities of both 8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenz(a)anthracene and a second uncharacterized derivative, Metabolite B, at low DMBA doses (<0.05 µg/ml medium) and primarily Metabolite B at higher DMBA doses (>0.05 µg/ml medium). Macrophages released the majority of the ethyl acetate-soluble metabolites that they produced into the surrounding medium. With the exception of 8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenz(a)anthracene, these derivatives were accumulated within tracheal and lung tissue when these organs were cocultivated with macrophages in the presence of DMBA.

¹ This work was suponsored by the National Cancer Institute under Contract N01-CO-25423 with Litton Bionetics, Inc., Frederick, Md.

² To whom requests for reprints should be addressed.

Received 10/ 5/77. Accepted 1/ 5/78.