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

Journal Article · Wed Sep 01 00:00:00 EDT 1982 · JNCI, J. Natl. Cancer Inst.; (United States)

OSTI ID:6160403

Wood, A W ^[1]; Levin, W; Chang, R L; Conney, A H; Slaga, T J; O'Malley, R F; Newman, M S; Buhler, D R; Jerina, D M

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1. Hoffman-La Roche Inc., Nutley, NJ

Eleven methyl- and/or fluorine-substitued benz(a)anthracenes were evaluated for tumor-initating activity on mouse skin. Outbred CD-1 and outbred Sencar mice received a single topical application of the hydrocarbons followed by twice weekly application 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-initator than 7- and 12-methylbenz(a)anthracene. Methyl substitution at the 7- and 7,12-positions of benz(a)anthracence 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 severalfold 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 substition of fluorine at the 5-position of 12-methylbenz(a)anthracene dramatically reduced their tumorigenic activity.

• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 6160403
• Journal Information: JNCI, J. Natl. Cancer Inst.; (United States), Vol. 69:3
• Country of Publication: United States
• Language: English

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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
HYDROCARBONS
BIOLOGICAL EFFECTS
METABOLIC ACTIVATION
TUMOR PROMOTERS
BENZANTHRACENE
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