Anticarcinogenic and cocarcinogenic effects of benzo[e]pyrene and dibenz[a,c]anthracene on skin tumor initiation by polycyclic hydrocarbons.
In the present study, we have examined the effects of benzo[e]pyrene (B[e]P) and dibenz[a,c]anthracene (DB[a,c]A) on the skin tumor-initiating activities of methylated and non-methylated polycyclic aromatic hydrocarbons (PAH). B[e]P, when applied 5 min prior to initiation with seven different PAH skin carcinogens, effectively inhibited the tumor-initiating activities of 7,12-dimethylbenz[a]anthracene (DMBA) and dibenz[a,h]anthracene (DB[a,h]A) but had little or no effect on the tumor-initiating activities of 3-methyl-cholanthrene (MCA), 7-methylbenz[a]anthracene (7-MBA), 12-methylbenz[a]anthracene (12-MBA), and 5-methyl-chrysene (5-MeC). B[e]P potentiated the tumor-initiating activity of benzo[a]pyrene (B[a]P) by approximately 30%, DB[a,c]A, when applied 5 min prior to initiation, inhibited the tumor-initiating activities of DMBA, MCA, and DB[a,h]A but had little or no effect on the tumor-initiating activities of B[a]P, 7-MBA, 12-MBA, and 5-MeC. DB[a,c]A, when applied 12, 24, or 36 h prior to initiation with B[a]P, which allowed time for induction of epidermal monooxygenase enzymes, inhibited tumor initiation. The covalent binding of DMBA and B[a]P to epidermal DNA was examined under the influence of B[e]P. Doses of 20 and 200 nmol B[e]P given 5 min prior to 10 nmol [3H]DMBA reduced binding to 47 and 22%, respectively, of the control value. In contrast, doses of 200 or 2000 nmol B[e]P given 5 min prior to 200 nmol [3H]B[a]P had little or no effect on total binding. The data indicate that one cannot predict anti and cocarcinogenic effects of B[e]P and DB[a,c]A on the basis of a presence or absence of a methyl substituent. In addition, fundamental differences exist in the processing and metabolism of DMBA and B[a]P by mouse epidermal cells.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D001551:Benz(a)Anthracenes / Q000494:pharmacology / Q000633:toxicity*; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D004247:DNA / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D008748:Methylcholanthrene / Q000633:toxicity; D051379:Mice; D008815:Mice, Inbred Strains; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000517:prevention & control
D001551:Benz(a)Anthracenes; D001580:Benzopyrenes; C016365:dibenzanthracenes; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA