Metabolism of 6-nitrobenzo[a]pyrene by hamster embryonic fibroblasts and its interaction with nuclear macromolecules

Incubation of 6-nitrobenzo[a]pyrene (6-nitroBaP) with hamster embryonic fibroblasts led to formation of both organic solvent-soluble and water-soluble products. High-pressure liquid chromatographic analysis of organic solvent-soluble extracellular metabolites showed the predominant presence of dihydrodoils, with only small amounts of phenolic products. This differed from microsomal metabolism, using hepatic preparations from 3-methylcholanthrene-pretreated rats, where a major phenolic peak was obtained. Subsequent treatment of aqueous layer with beta-glucuronidase, however, revealed that most of the phenols were associated with glucuronic acid to form water soluble products. Interaction of 6-nitroBaP with nuclear macromolecules from HEF was also studied. The chemical interacted with both DNA and RNA, but the specific activity was highest with nuclear proteins. This binding profile was found to be similar to that when benzo[a]pyrene was used, although the affinity toward protein binding was slightly higher for 6-nitroBaP.