Anticarcinogenic and cocarcinogenic effects of benzo[e]pyrene and dibenz[a,c]anthracene on skin tumor initiation by polycyclic hydrocarbons

John Digiovanni, Jerry Rymer, Thomas J. Slaga, R. K. Boutwell

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Abstract

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 nonmethylated polycyclic aromatic hydrocarbons (PAH). B[e]P, when applied 5 min prior to initiation with seven different PAH skin carcinogens, effectively inhibited the tumorinitiating 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-methylcholanthrene (MCA), 7-methylbenz[a]anthracene (7-MBA), 12-methylbenz[a]anthracene (12-MBA), and 5-methylchrysene (5-MeC). B[e]P potentiated the tumor-initiating activity of benzo[a]pyrene (B[a]P) by ∼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.

Original languageEnglish (US)
Pages (from-to)371-375
Number of pages5
JournalCarcinogenesis
Volume3
Issue number4
DOIs
StatePublished - Dec 1 1982
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research

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