Fluorine Substitution as a Probe for the Role of the 6-Position of Benzo[a]pyrene in Carcinogenesis

• Published in: JNCI : Journal of the National Cancer Institute 1983-08, Vol.71 (2), p.309-315
• Main Authors: Buening, Mildred K., Levin, Wayne, Wood, Alexander W., Chang, Richard L., Agranat, Israel, Rabinovitz, Mordecai, Buhler, Donald R., Mah, He Duck, Hernandez, Oscar, Simpson, Richard B., Jerina, Donald M., Conney, Allan H., Miller, Elizabeth C., Miller, James A.
• Format: Article
• Language: English
• Subjects: Animals; Benzo(a)pyrene; Benzopyrenes - toxicity; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Carcinogens - toxicity; Chemical agents; Female; Liver Neoplasms, Experimental - chemically induced; Liver Neoplasms, Experimental - pathology; Lung Neoplasms - chemically induced; Lung Neoplasms - pathology; Male; Medical sciences; Mice; Neoplasms, Experimental - pathology; Papilloma - chemically induced; Papilloma - pathology; Rats; Sarcoma, Experimental - chemically induced; Sarcoma, Experimental - pathology; Sex Factors; Skin Neoplasms - chemically induced; Skin Neoplasms - pathology; Species Specificity; Tumors
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/71.2.309

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 adenomas in Swiss Webster mice treated before weaning. The 6-fluoro derivative, however, had about 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 of the hydrocarbons and for the induction of sarcomas 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 Fischer 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.