MICROSOMAL AND NUCLEAR-METABOLISM OF 3-METHYLCHOLANTHRENE

Hepatic nuclei and microsomes prepared from rats pretreated with 3-methyleholanthrene, or hepatic nuclei prepared from untreated rats, were incubated with generally 3H-labeled 3-methylcholanthrene in the presence of an NADPH-generating system. The metabolic products formed by these three systems were analyzed by high pressure liquid Chromatographie techniques and the products were comparable, both qualitatively and quantitatively. The metabolic formation, from both nuclei and microsomes, of radioactive products corresponding to the cis-1,2- and 11,12-diol,the trans-4,5-,9,10-and 11,12-dihydrodiol,and the 1-and 2-hydroxy and 1- and 2-ketone derivatives of 3-methyleholanthrene was observed when these metabolites were compared, on high pressure liquid chromatographs, with authentic compounds. Pretreatment of the rats with 3-methyleholanthrene resulted in a marked increase in nuclear metabolism, particularly in the formation of 2-hydroxy-3-methylcholanthrene. These studies further reinforce the importance of the nucleus in the metabolic activation of polycyclic hydrocarbons. © 1979.