苯并(a)蒽的五种二氢二醇对小鼠皮肤的致瘤性：苯并(a)蒽3,4 -二氢二醇的异常活性。
Tumorigenicity of five dihydrodiols of benz(a)anthracene on mouse skin: exceptional activity of benz(a)anthracene 3,4-dihydrodiol.
作者信息
Wood A W, Levin W, Chang R L, Lehr R E, Schaefer-Ridder M, Karle J M, Jerina D M, Conney A H
出版信息
Proc Natl Acad Sci U S A. 1977 Aug;74(8):3176-9. doi: 10.1073/pnas.74.8.3176.
Benz[a]anthracene and the five metabolically possible vicinal trans dihydrodiols of benz[a]anthracene were tested for ability to initiate skin tumors in CD-1 female mice. A single topical application of 0.4-2.0 mumol of hydrocarbon was followed 18 days later by twice weekly applications of the skin promoter 12-O-tetradecanoylphorbol-13-acetate. Comparisons of latency period, percent of mice with tumors, and number of papillomas observed per mouse indicated that benz[a]anthracene 1,2-, 5,6-, 8,9-, and 10, 11-dihydrodiols were all less active tumor initiators than was benz[a]anthracene. The high tumorigenicity of benz[a]anthracene 3,4-dihydrodiol, presumably the result of metabolism to either or both of the diastereomeric benz[a]anthracene 3,4-diol-1,2-epoxides, supports the bay region theory of polycyclic hydrocarbon carcinogenicity and provides the first example of a proximate carcinogenic metabolite that is much more active than the parent hydrocarbon on mouse skin.
对苯并[a]蒽及其五种代谢可能产生的邻位反式二氢二醇进行了测试，以评估它们在CD-1雌性小鼠中引发皮肤肿瘤的能力。单次局部涂抹0.4 - 2.0微摩尔的碳氢化合物，18天后，每周两次涂抹皮肤促癌剂12 - O - 十四烷酰佛波醇-13 - 乙酸酯。对潜伏期、患肿瘤小鼠的百分比以及每只小鼠观察到的乳头状瘤数量进行比较，结果表明苯并[a]蒽1,2 -、5,6 -、8,9 -和10,11 -二氢二醇作为肿瘤引发剂的活性均低于苯并[a]蒽。苯并[a]蒽3,4 -二氢二醇的高致瘤性，可能是代谢为非对映异构的苯并[a]蒽3,4 -二醇-1,2 -环氧化物中的一种或两种的结果，这支持了多环烃致癌性的湾区理论，并提供了第一个实例，即一种直接致癌代谢物在小鼠皮肤上比母体碳氢化合物活性高得多。
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