The comparative mutagenicity toward Salmonella typhlmurlum TA 100, tumor-inltlating and complete carcinogenic activity on mouse skin, and In vitro metabolism of fluorinated derivatives of the carcinogen 5-methylchrysene (5-MeC) were studied. The compounds studied were 1-fluoro-5-methyichrysene (1-F-5-MeC), 3-fiuoro-5-methylchrysene (3-F-5-MeC), 6-fluoro-5-methylchrysene (6-F-5-MeC), 7-fluoro-5-methylchrysene (7-F-5-MeC), 9-fluoro-5-methylchrysene (9-F-S-MeC), 11-fluoro-5-meth-ylchrysene (11-F-5-MeC), and 12-fluoro-5-methyichrysene (12-F-5-MeC). All seven fluoro compounds and 5-MeC were mutagenic toward S. typhlmurlum TA 100 when tested in the presence of liver homogenates from F344 rats treated with Arocior 1254; the most mutagenic compound was 7-F-5-MeC. In the assays for tumor-lnitiatlng activity on skin of Swiss mice, 1-F-5-MeC and 3-F-5-MeC were significantly less active than was 5-MeC at both doses studied (30 and 100 fig), whereas 12-F-5-MeC was less tumorlgenlc than was 5-MeC at the 30-μg dose only. The other fluorinated compounds were as active as 5-MeC as tumor initiators. In agreement with these results, both 1-F-5-MeC and 3-F-5-MeC were Inactive as complete carcinogens; 12-F-5-MeC was also significantly less carcinogenic than was S-MeC. 6-F-5-MeC was more carcinogenic than was 5-MeC, whereas 7-F-5-MeC, 9- F-S-MeC, and 11-F-5-MeC were as active as was 5-MeC. Examination of the In vitro metabolism of the fluorinated compounds by liver homogenates from Arocior 1254-treated rats indicated that fluorine substitution inhibited the oxidative metabolism at the position of attachment and at neighboring positions. Thus in 1-F-S-MeC and 3-F-5-MeC, formation of the 1,2-dlhydrodiol was inhibited and In 7-F-5-MeC, formation of the 7,8-dlhydrodiol and chrysenols was reduced. In the metabolism of 12-F-S-MeC, the concentration of the 1,2-dihydrodlol was reduced compared to that of 5-MeC, whereas In 6-F-5-MeC, formation of the 7,8-dihydrodlol and chrysenols was inhibited.
Bibliographical noteFunding Information:
I Received December 18, 1978; accepted March 19, 1979. 2 Supported by Public Health Service grant CAOl2376 from the National Cancer Institute. 3 Publication No. 16 in "A Study of Chemical Carcinogenesis." • Divisions of Environmental Carcinogenesis and Experimental Pathology, Naylor Dana Institute for Disease Prevention, American Health Foundation, Dana Rd., Valhalla, N.Y. 10595. S Recipient of Public Health Service career development award 5K04-CAOOI24 from the National Cancer Institute.