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A Comparison of Benzo(a)pyrene Metabolism by Liver and Lung Microsomal Enzymes from 3-Methylcholanthrene-treated Rhesus Monkeys and Rats

Battelle Columbus Laboratories, Columbus, Ohio 43201

The metabolism of benzo(a)pyrene by liver and lung microsomes from rats and rhesus monkeys was compared after 3-methylcholanthrene (3-MC) treatment. As with other species, lung activity in both the rhesus and rat showed a greater percentage increase from 3-MC treatment than did the respective liver activities. Rat lung and liver activity were increased to a greater extent than were rhesus lung and liver activity. The metabolites formed by both tissues from the two animal species were separated by high-pressure liquid chromatography and quantitated by liquid scintillation spectrometry. Treatment with 3-MC caused shifts in the metabolite ratios in rat and rhesus lung profiles, resulting in the appearance of an unknown which eluted between the 9,10- and 4,5-dihydrodihydroxybenzo(a)pyrene (diol) fractions. The 9,10- and 7,8-diol fractions formed by rat liver and rhesus lung were increased to a greater degree than were other metabolite fractions, as a result of 3-MC treatment. In the rat lung the benzo(a)pyrene-1,6 dione fraction increased over 60 times, and the 9-hydroxybenzo(a)pyrene fraction increased over 50 times after 3-MC treatment.

The most pronounced increases in relative metabolite ratios resulting from 3-MC treatment were observed for the 9,10- and 7,8-diol fractions from rhesus lung and rat liver microsomal assays. In contrast, the 4,5-diol ratios from rat liver and rhesus lung decreased substantially as a result of treatment with 3-MC.

¹ To whom requests for reprints should be addressed.

Received 2/17/77. Accepted 6/ 7/77.