TUMOR-INITIATING ACTIVITY ON MOUSE SKIN OF BAY-REGION DIOL-EPOXIDES OF 5,6-DIMETHYLCHRYSENE AND BENZO[C]PHENANTHRENE

被引:28
作者
AMIN, S
DESAI, D
HECHT, SS
机构
[1] Division of Chemical Carcinogenesis, American Health Foundation, Valhalla, NY 10595
关键词
D O I
10.1093/carcin/14.10.2033
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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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页码:2033 / 2037
页数:5
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