Comparative tumor initiating activities of cyclopentano and methyl derivatives of 5-methylchrysene and chrysene.
Previous studies showed that 5,6-dimethylchrysene (5,6-diMeC) and 5,7-diMec were significantly less tumorigenic than 5-methylchrysene (5-MeC). These results were unexpected based on the known mechanism of metabolic activation of 5-MeC and indicated the presence of critical steric requirements for tumorigenicity at the 6 and 7 positions of 5-MeC. In this study, the structure activity relationships were further extended by comparing the tumor-initiating activities on mouse skin of 5-MeC, 6,7-cyclopentano-5-MeC, 5,6-diMeC, 6,7-diMeC, 5,7-diMeC, chrysene and 6,7-cyclopentanochrysene. 5-MeC was the most tumorigenic compound, with activity significantly higher than all other compounds tested. Among the other compounds. Only 5,6-diMeC was significantly tumorigenic. The results demonstrate that substitution of methyl or methylene groups at the 6 or 7 positions of 5-MeC leads to a significant reduction of tumor initiating activity.
Amin
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American Health Foundation, Valhalla, NY 10595.
Hecht
S S
SS
Di Raddo
P
P
Harvey
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RG
D000818:Animals; D001711:Biotransformation; D002273:Carcinogens; D055598:Chemical Phenomena; D002621:Chemistry; D002911:Chrysenes / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D051379:Mice; D010616:Phenanthrenes / Q000633:toxicity*; D012878:Skin Neoplasms / Q000139:chemically induced; D013329:Structure-Activity Relationship
D002273:Carcinogens; D002911:Chrysenes; D010616:Phenanthrenes; C064130:6,7-cyclopentano-5-methylchrysene; C043380:5,6-dimethylchrysene; C064131:6,7-cyclopentanochrysene; C021977:chrysene,2-diol-3,4-epoxide-1; C008422:5-methylchrysene