Metabolism of benzo[a]pyrene by cultured rat and human buccal mucosa cells

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Abstract
Primary cultures of epithelial and fibroblast cells derived from human oral mucosa were studied for the ability to activate a tobacco smoke carcinogen, benzo[a]pyrene (BP). The cells were exposed to benzo[a]pyrene for 18 h. The cell-free medium was extracted with ethylacetate/acetone, and high-pressure liquid chromatography analysis of this fraction revealed that BP tetrols and diols were the major metabolites formed by both epithelial and fibroblast cells. However, the epithelial cells had a much higher rate of biotransformation of BP as measured by binding to cellular DNA. The mean binding level to human buccal mucosal DNA was among the highest observed in stratified human epithelia. The major BP - DNA adduct was formed by the reaction of the ‘bay-region’ BP diolepoxide with the exocyclic 2-amino group in guanine. In contrast to human cells, BP phenols and BP 9, 10-diol were the major metabolites produced by primary epithelial and fibroblast cells derived from rat buccal mucosa. The DNA binding levels of BP in the two rat cell types were identical, and the binding level was several-fold lower than in the human epithelial cells. When an established rat tongue epithelial cell line (RTE 2) was treated with polycyclic aromatic hydrocarbons - BP and 7,12-dimethylbenz[a]-anthracene - a slight toxic effect was observed. Our results indicate that primary cultures of oral mucosa are able to metabolize BP into its ultimate carcinogenic form at a rate similar to or higher than other potential target tissues for BP-induced carcinogenesis.