The discrepancy between in vivo and in vitro experiments with polycyclic aromatic hydrocarbon(PAH) carcinogens: a hypothetical explanation

The hypothesis suggested in this paper is an attempt to explain a discrepancy between in vivo and in vitro polycyclic aromatic hydrocarbons (PAH)-carcinogenesis experiments, described frequently in the literature. Whereas, in pretreated animals, a higher level of induced PAH-metabolizing enzymes reduces PAH-carcinogenicity, in the tissues or homogenates from pretreated animals the induced PAH-metabolizing enzymes increase the carcinogenic effects of PAH. In our model, both the pretreatment or route of administration should cause a frameshift in the alternation of active and inactive metabolites in the compartments. In pretreated animals the carcinogenicity of PAH administered per os is reduced, because the PAH metabolism is completed to tetrol, the ultimate inactive metabolite, before it reaches the target tissue. The hypothesis explains the discrepancy and makes predictions which can be tested experimentally.