Metabolism and DNA binding of benzo[a]pyrene in cultured human bladder and bronchus.

The metabolism of benzo[a]pyrene (BP) was examined in explant cultures of human bladder and bronchus. Three-day cultures were exposed to radiolabeled BP for 24 h, and the metabolism was determined by analysis of the level of binding of reactive metabolites to DNA, and by the release of metabolites into the medium. For a given individual, the DNA binding level and extent of metabolism was usually higher in the bladder than in the bronchus. In specimens obtained from 16 individuals, the average DNA-binding levels for BP-DNA adducts following a 24 h exposure to 1 microM BP were 6.4 +/- 5.0 mumol BP/mol deoxyribonucleotide for the bladder and 3.1 +/- 1.9 mumol BP/mol deoxyribonucleotide for the bronchus. The major BP-DNA adduct in both tissues co-chromatographed with one of the adducts formed by reaction of r-7, t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene with deoxyguanosine using high-pressure liquid chromatography. In tissues obtained from the same individual, the binding levels of BP metabolites to bladder cell DNA was not strongly correlated to that of bronchial cell DNA (r = 0.55). The medium of both tissues contained small amounts of free, unconjugated metabolites of BP (less than 3% of the total) and large amounts (30-86% of the total) of unidentified, highly polar material. Human bladder appears to be the most active explant tissue yet studied with respect to its ability to activate BP to DNA binding forms. The relevance of this observation to human bladder cancer is, as yet, unknown.