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), Journal Name: JNCI, J. Natl. Cancer Inst.; (United States) Vol. 69:3; ISSN JJIND
• Country of Publication: United States
• Language: English

Related Subjects

560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AROMATICS
BENZANTHRACENE
BIOLOGICAL EFFECTS
BODY
CARCINOGENESIS
CARCINOGENS
CONDENSED AROMATICS
DIMETHYLBENZANTHRACENE
ESTERS
HYDROCARBONS
MAMMALS
METABOLIC ACTIVATION
MICE
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PHORBOL ESTERS
PROMOTERS
RODENTS
SKIN
TUMOR PROMOTERS
VERTEBRATES