Metabolism of Phenanthrene, Benz[a]anthracene, Benzo[a]pyrene, Chrysene and Benzo[c]phenanthrene by Eight cDNA-expressed Human and Rat Cytochromes P450

Phenanthrene, benz[a]anthracene, chrysene, benzo[c]phenanthrene, and benzo[a]pyrene have been studied for their regiospecific oxidation by five human (1A1, 1A2, 2A6, 2E1, 3A4) and three rat (1A1, 1A2, 2B1) CYP isoforms. All substrates are preferentially metabolized by CYP1A1 and CYP1A2 in human and rat. Other isoforms play a minor role if at all. Significant differences between human and rat CYP isoforms can be recognized with regard to the regiospecific oxidation of PAH. For instance, K-region oxidation is more pronounced in rat than in human CYP1A1 and CYP1A2. Hence, extrapolation from metabolism studies in rodents to human may be limited.