Tumor-initiating activity on mouse skin of bay region diol-epoxides of 5,6-dimethylchrysene and benzo[c]phenanthrene.
Previous metabolism and DNA-binding studies indicated that 5,6-dimethylchrysene (5,6-diMeC) is metabolically activated in mouse skin through formation of its 1,2-dihydrodiol (5,6-diMeC-1,2-diol) and bay region diol-epoxide (anti-5,6-diMeC-1,2-diol-3,4-epoxide). These metabolites were tested as tumor initiators on mouse skin. Included for comparison were syn-5,6-diMeC-1,2-diol-3,4-epoxide and anti-4,3-dihydroxy-2,1-epoxy- 4,3,2,1-tetrahydrobenzo[c]phenanthrene (anti-B[c]Ph-4,3-diol-2,1-epoxide). At an initiating dose of 100 nmol/mouse, 5,6-diMeC-1,2-diol and anti-5,6-diMeC-1,2-diol-3,4-epoxide were significantly more tumorigenic than 5,6-diMeC, inducing 7.1 and 3.9 skin tumors per mouse respectively compared to 1.1 induced by 5,6-diMeC. Similar results were obtained at an initiating dose of 33 nmol/mouse. This is the first example of a methylated polynuclear aromatic hydrocarbon bay region diol-epoxide which is more tumorigenic than its parent hydrocarbon on mouse skin. syn-5,6-diMeC-1,2-diol-3,4-epoxide was only weakly tumorigenic. Comparisons of anti-5,6-diMeC-1,2-diol-3,4-epoxide and anti-B[c]Ph-4,3-diol-2,1-epoxide demonstrated that the latter was a stronger tumor initiator. The results of this study confirm the bay region diol-epoxide metabolic activation pathway of 5,6-diMeC but do not provide an explanation for the relatively weak tumorigenicity of this hydrocarbon on mouse skin.
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Division of Chemical Carcinogenesis, American Health Foundation, Valhalla, NY 10595.
Desai
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Hecht
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D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism*; D002911:Chrysenes / Q000378:metabolism*; D005260:Female; D051379:Mice; D010616:Phenanthrenes / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*
D002273:Carcinogens; D002911:Chrysenes; D010616:Phenanthrenes; C083912:1,2-dihydro-1,2-dihydroxy-5,6-dimethychrysene; C075956:1,2-dihydroxy-5,6-dimethyl-3,4-epoxy-1,2,3,4-tetrahydrochrysene; C043380:5,6-dimethylchrysene; C002615:benzo(c)phenanthrene