Tumorigenicity of 6-halogenated derivatives of benzo[a]pyrene in mouse skin and rat mammary gland.
Studies of the tumorigenicity of 6-halogenated derivatives of benzo[a]pyrene (BP) can provide evidence about the role of the 6 position in the carcinogenic activation of BP. Female Swiss and A-strain mice were treated on the skin with BP, 6-fluorobenzo[a]pyrene (6-FBP), 6-chlorobenzo[a]pyrene (6-C1BP), 6-bromobenzo[a]pyrene (6-BrBP) and 6-iodobenzo[a]pyrene (6-IBP) by repeated application, and in some cases by initiation-promotion. While BP was more potent than 6-FBP, only these two compounds exhibits tumor-initiating and carcinogenic activity in mouse skin. Female Sprague-Dawley rats were treated with BP, 6-FBP, 6-ClBP, and 6-BrBP by intramammillary injection. BP and 6-FBP induced high levels of mammary epithelial tumors and fibrosarcomas. 6-ClBP elicited only a high percentage of fibrosarcomas, whereas 6-BrBP induced a few adenocarcinomas. These results indicate that chloro or bromo substitution at C-6 in BP reduces or eliminates carcinogenic activity. Conversely, 6-FBP, from which the fluoro substituent has been chemically and metabolically removed by one-electron oxidation, displays a moderate carcinogenic activity which is consistent with activation by either one-electron oxidation or monooxygenation.
Cavalieri
E
E
Eppley Institute for Research in Cancer, Omaha, NE.
Rogan
E
E
Cremonesi
P
P
Higginbotham
S
S
Salmasi
S
S
D000818:Animals; D001564:Benzo(a)pyrene / Q000031:analogs & derivatives* / Q000378:metabolism; D005609:Free Radicals; D006846:Hydrocarbons, Halogenated / Q000633:toxicity; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced*; D051379:Mice; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012878:Skin Neoplasms / Q000139:chemically induced*; D013329:Structure-Activity Relationship
D005609:Free Radicals; D006846:Hydrocarbons, Halogenated; D001564:Benzo(a)pyrene