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.