title: Skin tumor initiating activities of the 9- and 10-fluoro derivatives of 7- or 12-methylbenz[a]anthracene and the 9- and 10-trifluoromethyl derivatives of 7,12-dimethylbenz[a]anthracene in SENCAR mice.
abstract: We have determined the skin tumor initiating activity in SENCAR mice of several 9- and 10-substituted mono- and dimethylbenz[a]anthracene derivatives. 9-fluoro-7-methylbenz[a]anthracene (9-F-7-MBA) was approximately as active as 7-MBA, whereas 10-F-7-MBA was considerably more active as a skin tumor initiator than the parent compound. Initiating doses of 200 and 400 nmol per mouse of 10-F-7-MBA yielded 14.17 +/- 0.16 and 22.47 +/- 1.64 papillomas per mouse after 18 weeks of promotion with 12-O-tetradecanoylphorbol-13-acetate, whereas comparable doses of 7-MBA yield 2.13 +/- 0.12 and 4.73 +/- 0.68 papillomas per mouse respectively. The effect of fluoro substituents at positions 9 and 10 of 12-MBA, a less potent tumor-initiator than 7-MBA, was also examined. 9-F-12-MBA was only slightly more active than 12-MBA, whereas 10-F-12-MBA was again considerably more active than the parent compound. Doses of 400 and 800 nmol per mouse of 10-F-12-MBA yielded 24.97 +/- 2.18 and 22.20 +/- 6.47 versus 1.13 +/- 0.80 and 3.00 +/- 0.17 papillomas per mouse respectively for comparable initiating doses of 12-MBA. The effect of introducing a trifluoromethyl (CF3) group at the 9 and 10 positions of 7,12-dimethylbenz[a]anthracene was also examined. A CF3 group at either of these positions essentially eliminated the tumor initiating activity of DMBA at the doses tested. These results when taken together with previous results from our laboratory suggest that electron donating substituents at positions 9 and 10 of the benz[a]anthracene nucleus either have no effect or enhance skin tumor initiating activity, whereas electron withdrawing groups at these positions dramatically reduce or abolish tumor initiating activity.
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives*; D000818:Animals; D001551:Benz(a)Anthracenes; D005260:Female; D005461:Fluorine; D051379:Mice; D012878:Skin Neoplasms / Q000139:chemically induced*; D013329:Structure-Activity Relationship
chemical_list: D001551:Benz(a)Anthracenes; D005461:Fluorine; D015127:9,10-Dimethyl-1,2-benzanthracene; C021220:12-methylbenzanthracene