Metabolism of chemical carcinogens by cultured human and rat bladder epithelial cells

Abstract

The metabolism of benzo[a]pyrene [BP], aflatoxin B1, N-nitrosodimethylamine, N-nitrosoethylmethylamine and N-nitrosopyrrolidine was studied in cultures of normal human and rat urinary bladder epithelial cells. The cultures were incubated with radioactively labeled carcinogens for 24 h. Only slight variation in binding level of BP to DNA among the 3 human bladder cell lines was seen, the level of binding being higher than to rat DNA. The major BP-DNA adduct (80%) in human bladder cells eluted prior to the adducts formed by reaction of 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydro-BP with guanine by high pressure liquid chromatography but has yet to be identified. The BP-DNA adducts were quickly removed and only .apprx. 10% of the radioactivity remained associated with human bladder DNA 72 h posttreatment with BP. The 7,8- and 9,10-diols of BP were the major organo-soluble metabolites formed by rat and human bladder cells. The primary BP metabolites were conjugated only to a minor extent. The highest level of DNA modification was seen with N-nitrosodimethylamine. N-Nitrosopyrrolidine was oxidized in the .alpha.- and .beta.-position by all 3 cell lines, the oxidation at the .alpha.-position being predominant. No binding to DNA was detectable with N-nitrosoethylmethylamine, although this compound was metabolized as measured by the formation of CO2 and aldehydes. The urinary bladder metabolizes chemical carcinogens into electropositive metabolites. Qualitative differences exist between the data from bladder cells and those from other human organs.