Mouse skin tumor initiating activity of 5-, 7-, and 12-methyl- and fluorine-substituted benz[a]anthracenes

A. W. Wood, W. Levin, R. L. Chang, A. H. Conney, T. J. Slaga, R. F. O'Malley, M. S. Newman, D. R. Buhler, D. M. Jerina

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

As an approach for elucidation of structure activity relationships that underlie the exceptionally large difference in carcinogenic activity between benz[a]anthracene and 7,12-dimethylbenz[a]anthracene (7,12-DMBA), 11 methyl- and/or fluorine-substituted benz[a]anthracenes were evaluated for tumor-initiating activity on mouse skin. Outbred CD-1 and outbred Sencar mice received a single topical application of the hydrocarbons followed by twice weekly applications of the tumor promoter 12-O-tetradecanoylphorbol 13-acetate for 16-26 weeks. 7,12-DMBA was almost two orders of magnitude more active as a tumor-initiator than 7- and 12-methylbenz[a]anthracene. Methyl substitution at the 7- and 7,12-positions of benz[a]anthracene was significantly more effective in the enhancement of tumorigenic activity than fluorine substitution at these positions. Although 7-fluorobenz[a]anthracene, 12-fluorobenz[a]anthracene, and 7,12-difluorobenz[a]anthracene had only 0.15, 0.26, and less than 0.005 times the tumor-initiating activity of their respective methyl-substituted derivatives, they were several fold more active than benz[a]anthracene. 7-Fluorobenz[a]anthracene was slightly less active than 12-fluorobenz[a]anthracene, whereas 7-methylbenz[a]anthracene was about twofold more active than 12-methylbenz[a]anthracene. For 7,12-disubstituted benz[a]anthracenes, 7-methyl-12-fluorobenz[a]anthracene was more than twice as tumorigenic as 7-fluoro-12-methylbenz[a]anthracene, but each was individually more active than 7-methylbenz[a]anthracene and 12-methylbenz[a]anthracene, respectively. Both fluorinated compounds were much less active than 7,12-DMBA. Substitution of fluorine or methyl at the 5-position of 7-methylbenz[a]anthracene and substitution of fluorine at the 5-position of 12-methylbenz[a]anthracene dramatically reduced their tumorigenic activity.

Original languageEnglish (US)
Pages (from-to)725-728
Number of pages4
JournalJournal of the National Cancer Institute
Volume69
Issue number3
StatePublished - Dec 4 1982
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Wood, A. W., Levin, W., Chang, R. L., Conney, A. H., Slaga, T. J., O'Malley, R. F., Newman, M. S., Buhler, D. R., & Jerina, D. M. (1982). Mouse skin tumor initiating activity of 5-, 7-, and 12-methyl- and fluorine-substituted benz[a]anthracenes. Journal of the National Cancer Institute, 69(3), 725-728.