The effects of weak or non-carcinogenic polycyclic hydrocarbons on 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene skin tumor-initiation.
Benzo[e]pyrene (B[e]P) inhibited 7,12-dimethylbenz[a]anthracene (DMBA) skin tumor-initiation in mice by 84%, whereas pyrene and fluoranthene inhibited DMBA initiation by 50 and 34%, respectively. However, B[e]P, pyrene and fluoranthene had either no significant effect or a slight enhancing effect on benzo[a]pyrene (B[a]P) skin tumor-initiation. In addition, B[e]P had essentially no effect on the initiating ability of (+/-)B[a]P-7 beta,8 alpha-diol-9 alpha,10 alpha-epoxide. As a tumor-initiator, B[e]P was found to have very weak activity at a 252 microgram/level (0.4 papillomas/mouse at 40 weeks) and no activity at 100 microgram. When given at a dose of 100 microgram twice weekly, B[e]P induced 2.1 papillomas/mouse at 30 weeks, and 25% of the mice had carcinomas at 40 weeks. However, B[e]P carcinogenic activity is weak when compared to B[a]P, which can induce a comparable tumor response at a dose of 5 microgram twice weekly. When B[e]P was tested as a tumor promoter at a dose of 100 microgram twice weekly after DMBA initiation, it induced 4.5 papillomas/mouse at 30 weeks and a 45% carcinoma incidence at 40 weeks, which was approximately twice as effective as B[e]P alone. The data show that B[e]P is a very weak tumor initiator, a weak complete carcinogen, a moderate tumor promoter, possibly a weak co-tumor-initiator when given with B[a]P, and a potent anit-tumor-initiator when given with DMBA. The anti-tumor initiating and co-tumor-initiating effects of B[e]P appear to be related to its ability to modify the conversion of the tumor initiator into an electrophilic intermediate(s) which are capable of covalently binding to DNA. In addition, B[e]P induced epidermal cellular proliferation which may be related to its promoting ability.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001551:Benz(a)Anthracenes / Q000494:pharmacology*; D001580:Benzopyrenes / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division; D003043:Cocarcinogenesis; D004247:DNA / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism / Q000503:physiopathology; D004852:Epoxy Compounds / Q000494:pharmacology; D005260:Female; D005449:Fluorenes / Q000494:pharmacology; D007249:Inflammation / Q000209:etiology; D051379:Mice; D011083:Polycyclic Compounds / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000139:chemically induced
D001551:Benz(a)Anthracenes; D001580:Benzopyrenes; D004852:Epoxy Compounds; D005449:Fluorenes; D011083:Polycyclic Compounds; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA