Fluorine substitution as a probe for the role of the 6-position of benzo[a]pyrene in carcinogenesis

The tumorigenic activities of benzo[a]pyrene (BP) and 6-fluorobenzo[a]pyrene (6-F-BP) were compared to determine whether an unsubstituted 6-position is important for the carcinogenic effect of BP. Highly purified samples of 6-F-BP and BP had similar activities for the induction of lung adenoma in Swiss Webster mice treated before weaning. The 6-fluoro derivative, however, had absolute one-half as much activity as BP for the initiation of skin papillomas in CD-1 mice. Similarly, 6-F-BP (~ 90% purity) had about one-half the activity of BP for the induction of skin tumors in C57BL/6J mice given repetitive treatments for the hydrocarbons and for the induction of sarcoma in C3H/fCum mice given a single sc injection. 6-F-BP (~ 90% purity) had activity similar to that of BP for induction of sarcomas at the sc injection site in Fisher 344 rats. These results and related data indicate the need for detailed metabolic studies whenever fluorine substitution is used as a probe to assess the role of the unsubstituted position in the carcinogenicity of the parent compound.