The role of trace metals in cytochrome P4501 regulation.

Trace metals and polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental co-contaminants and the trace metals could influence the carcinogenicity of the PAHs by altering their extent of induction of cytochromes P4501A1, 1A2, and 1B1 (CYP). Studies in cell lines from humans, rodents, chickens, and fish, and in cell culture generally indicate that trace metals diminish the inductive potency of PAHs for these CYPs. The extent of the effect is species-, metal-, PAH-, and metal dose-dependent. Both transcriptional and post-translational mechanisms are involved in the trace metal-mediated down regulation of the CYP1 forms. The latter mechanism incorporates induction of heme oxygenase-1 by the metals, with resultant heme catabolism. Thus, trace metals could diminish the carcinogenicity of PAHs.