Metabolic activations of polycyclic hydrocarbons. Structure-activity relationships.

Considerable evidence now points to 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrenes as ultimate mutagenic and carcinogenic forms of benzo(a)-pyrene. Quantum mechanical calculations have been performed to assess the possible general role of diol epoxides in polycyclic aromatic hydrocarbon (PAH) mutagenesis and carcinogenesis. The calculations enable a prediction of relative reactivity (ease of carbonium ion formation) for diol epoxides derived from a single PAH and also for diol epoxides from different PAHs. The calculated reactivity has so far been found to provide a good estimate of diol epoxide mutagenicity. Results of the metabolic activation of benzo(a)anthracene dihydrodiol derivatives and of the mutagenicity of benzo(a)anthracene diol epoxides are reported. Limitations inherent in predictions of polycyclic aromatic hydrocarbon carcinogenicity using a model based upon the calculated reactivity of a potential metabolite are discussed.