Abstract |
The major dihydrodiols formed from 5-methylchrysene by rat liver 9000 X g supernatant were tested for tumor-initiating activity on mouse skin. The compounds tested were 1,2-dihydro-1,2-dihydroxy-5-methylchrysene, 7,8-dihydro-7,8-dihydroxy-5-methylchrysene, 9,10-dihydro-9,10-dihydroxy-5-methylchrysene, and 5-methylchrysene. Each compound was applied in a total initiating dose of 30 microgram and was followed by promotion with tetradecanoylphorbol acetate. 1,2-Dihydro-1,2-dihydroxy-5-methylchrysene was the most powerful tumor initiator, inducing tumors in 95% of the animals and 7.3 tumors per animal. 5-Methylchrysene and 7,8-dihydro-7,8-dihydroxy-5-methylchrysene induced tumors in 75 and 50% of the animals and gave 3.0 and 1.1 tumors per animal, respectively. 9,10-Dihydro-9,10-dihydroxy-5-methylchrysene was not tumorigenic. The results indicate that 1,2-dihydro-1,2-dihydroxy-5-methylchrysene is a major proximate carcinogen of 5-methylchrysene. Both 1,2-dihydro-1,2-dihydroxy-5-methylchrysene and 7,8-dihydro-7,8-dihydroxy-5-methylchrysene can theoretically form bay-region dihydrodiol epoxides, but the former was more tumorigenic than the latter. The high activity of 1,2-dihydro-1,2-dihydroxy-5-methylchrysene is typical of hydrocarbon derivatives with a methyl group in the bay region adjacent to an unsubstituted angular ring.
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Authors | S S Hecht, A Rivenson, D Hoffmann |
Journal | Cancer research
(Cancer Res)
Vol. 40
Issue 5
Pg. 1396-9
(May 1980)
ISSN: 0008-5472 [Print] United States |
PMID | 7370979
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Carcinogens
- Chrysenes
- Phenanthrenes
- 1,2-dihydro-1,2-dihydroxy-5-methylchrysene
- 9,10-dihydro-9,10-dihydroxy-5-methylchrysene
- 7,8-dihydro-7,8-dihydroxy-5-methylchrysene
- 5-methylchrysene
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Topics |
- Animals
- Biotransformation
- Carcinogens
(metabolism)
- Carcinoma
(chemically induced)
- Chrysenes
(metabolism)
- Dose-Response Relationship, Drug
- Female
- Mice
- Neoplasms, Experimental
(chemically induced)
- Papilloma
(chemically induced)
- Phenanthrenes
(metabolism)
- Skin Neoplasms
(chemically induced)
- Structure-Activity Relationship
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