Metabolism of benzo[a]pyrene in human skin xenografts

Although a human neonatal foreskin graft to a nude mouse has been shown to be morphologically intact for several months after establishment, the feasibility of using this system for carcinogenesis studies has not been widely investigated. In this study, we have investigated the metabolism of benzo[a]pyrene (BaP) in human skin xenografts after the topical application of different concentrations of [3H]BaP (0.5 microgram-10.0 micrograms and 20 muCi/graft) for 2 h and 1.0 micrograms [3H]BaP for various intervals of time up to 4 h. Significant amounts of different organic solvent soluble metabolites were observed in all the different samples. The increase in the amounts of the organic solvent soluble metabolites was linear over the 0.5 microgram to 5.0 micrograms/graft range. When 1.0 microgram [3H]BaP was applied to each graft, the maximum production of the organic solvent soluble metabolites was observed 10 minutes after treatment and it then decreased with time. Diols were the major metabolites detected in each of the experiments, followed by phenols, and then tetrols. The levels of water soluble glucuronide and sulfate conjugates were almost equivalent for each treatment over the same range of application of BaP per graft. The combined levels of these conjugates and the non-extractable organic soluble metabolites in the residue, generally ranged between 7-24% of the total metabolites in the various experiments.