Wislocki P G, Kapitulnik J, Levin W, Lehr R, Schaefer-Ridder M, Karle J M, Jerina D M, Conney A H
Cancer Res. 1978 Mar;38(3):693-6.
Benz[a]anthracene and the five metabolically possible trans-dihydrodiols of benz[a]anthracene were tested for carcinogenicity in newborn Swiss-Webster mice. Four hundred, 800, and 1600 nmoles hydrocarbon i.p. were sequentially injected on Days 1, 8, and 15 of life. The mice were killed at 22 weeks of age. Of the mice treated with trans-3,4-dihydroxy-3, 4-dihydrobenz[a]anthracene, 24% developed malignant lymphoma, whereas 4% of the animals treated with benz[a]anthracene had malignant lymphoma. None of the animals treated with the trans-1,2-dihydroxy-1,2-dihydrobenz[a]anthracene, trans-5,6-dihydroxy-5,6-dihydrobenz[a]anthracene, trans-8,9-dihydroxy-8,9-dihydrobenz[a]anthracene, or trans-10,11-dihydroxy-10,11-dihydrobenz[a]anthracene had malignant lymphoma. trans-3,4-Dihydroxy-3,4-dihydrobenz[a]anthracene caused about 35-fold more pulmonary adenomas than did benz[a]anthracene, whereas the trans-1,2-dihydroxy-1,2-dihydrobenz[a]anthracene, trans-5,6-dihydroxy-5,6-dihydrobenz[a]anthracene, trans-8,9-dihydroxy-8,9-dihydrobenz[a]anthracene, and trans-10, 11-dihydroxy-10,11-dihydrobenz[a]anthracene had little or no activity. The exceptionally high carcinogenicity of trans-3,4-dihydroxy-3,4-dihydrobenz[a]anthracene is consistent with the metabolism of this compound to either or both of the diastereomeric bay region 3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenz[a]anthracenes, and the data support the bay region theory of polycyclic hydrocarbon carcinogenesis.
对苯并[a]蒽及其五种代谢可能产生的反式二氢二醇进行了新生瑞士-韦伯斯特小鼠致癌性测试。在出生后第1、8和15天，依次腹腔注射400、800和1600纳摩尔的碳氢化合物。小鼠在22周龄时处死。经反式-3,4-二羟基-3,4-二氢苯并[a]蒽处理的小鼠中，24%发生了恶性淋巴瘤，而经苯并[a]蒽处理的动物中有4%发生了恶性淋巴瘤。经反式-1,2-二羟基-1,2-二氢苯并[a]蒽、反式-5,6-二羟基-5,6-二氢苯并[a]蒽、反式-8,9-二羟基-8,9-二氢苯并[a]蒽或反式-10,11-二羟基-10,11-二氢苯并[a]蒽处理的动物均未发生恶性淋巴瘤。反式-3,4-二羟基-3,4-二氢苯并[a]蒽引起的肺腺瘤比苯并[a]蒽多约35倍，而反式-1,2-二羟基-1,2-二氢苯并[a]蒽、反式-5,6-二羟基-5,6-二氢苯并[a]蒽、反式-8,9-二羟基-8,9-二氢苯并[a]蒽和反式-10,11-二羟基-10,11-二氢苯并[a]蒽几乎没有活性或无活性。反式-3,4-二羟基-3,4-二氢苯并[a]蒽极高的致癌性与该化合物代谢为非对映体湾区3,4-二羟基-1,2-环氧-1,2,3,4-四氢苯并[a]蒽中的一种或两种一致，数据支持多环烃致癌作用的湾区理论。
