Tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland of fluorinated derivatives of benzo[a]pyrene and 3-methylcholanthrene.
Comparative studies of tumor-initiating activity in mouse skin and carcinogenicity in rat mammary gland were conducted with benzo[a]pyrene (BP) and 3-methylcholanthrene (MC) derivatives. SENCAR mice were initiated with BP, 6-fluorobenzo[a]pyrene (6-FBP), 6-methylBP, 7-FBP, 8-FBP, 9-FBP, 10-FBP, or 10-azaBP and promoted with tetradecanoyl phorbol acetate. The same compounds plus BP 7,8-dihydrodiol were tested by intramammillary injection in female Sprague-Dawley rats. Tumor-initiating activity in mice and/or carcinogenicity in rats were observed for BP, 6-methylBP, 6-, 7-, 8-, and 10-FBP, whereas 9-FBP was inactive in both experiments and 10-azaBP was only marginally active in the mammary gland. BP 7,8-dihydrodiol was carcinogenic in rat mammary gland, although it was less potent than BP. MC, 8-FMC, 10-FMC, and 3-methylcholanthrylene were also tested in Sprague-Dawley rats by intramammillary injection. All compounds were carcinogenic, with MC displaying the most potent activity. The less potent carcinogenic activity of BP 7,8-dihydrodiol in the mammary gland, compared with BP, and the moderate-to-weak tumor-initiating and/or carcinogenic activity of 7-, 8-, and 10-FBP suggest that the bay-region diol-epoxide pathway does not play a significant role in the activation of BP in these two target tissues. Similarly, the carcinogenic activity of 8-FMC and 10-FMC, in which the bay-region diol-epoxide pathway is blocked, suggests that this mechanism of activation is not important in the carcinogenicity of MC in rat mammary gland.
Cavalieri
E
E
Eppley Institute for Research in Cancer, Omaha, NE.
Rogan
E
E
Higginbotham
S
S
Cremonesi
P
P
Salmasi
S
S
D000818:Animals; D001564:Benzo(a)pyrene / Q000031:analogs & derivatives* / Q000378:metabolism; D001711:Biotransformation; D005260:Female; D006845:Hydrocarbons, Fluorinated / Q000378:metabolism / Q000633:toxicity; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced*; D008748:Methylcholanthrene / Q000031:analogs & derivatives* / Q000378:metabolism; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D012878:Skin Neoplasms / Q000139:chemically induced*; D013329:Structure-Activity Relationship
D006845:Hydrocarbons, Fluorinated; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene