Kapitulnik J, Wislocki P G, Levin W, Yagi H, Thakker D R, Akagi H, Koreeda M, Jerina D M, Conney A H
Cancer Res. 1978 Sep;38(9):2661-5.
Optically pure (+)- and (-)-trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrenes [(+)- and (-)-BP 7,8-dihydrodiol] were tested for carcinogenicity by giving newborn mice i.p. injections of 20, 40, and 80 nmol of compound on Days 1, 8, and 15 of life. The animals were killed at 17 weeks of age. Control mice had 0.10 pulmonary adenoma per mouse, whereas animals treated with (+)-BP 7,8-dihydrodiol and (-)-BP 7,8-dihydrodiol had 0.16 and 9.28 pulmonary adenomas per mouse, respectively. When a 5-fold higher dose was administered according to the above dosage schedule, (+)-dihydrodiol caused 2.34 pulmonary adenomas per mouse and (-)-BP 7,8-dihydrodiol caused 32.2 pulmonary adenomas per mouse. When 200, 400, and 800 nmol of benzo(a)pyrene or (+)-BP 7,8-dihydrodiol were administered sequentially on Days 1, 8, and 15 of life, 4.13 and 18.5 pulmonary adenomas per mouse, respectively, were observed when the mice were 17 weeks of age. This high dose of (-)-BP 7,8-dihydrodiol killed most of the mice. Administration of (-)-BP 7,8-dihydrodiol caused a high incidence of malignant lymphomas, whereas (+)-BP 7,8-dihydrodiol and benzo(a)pyrene had little or no ability to cause malignant lymphomas.
通过在新生小鼠出生后第1、8和15天腹腔注射20、40和80 nmol的化合物,对光学纯的(+)-和(-)-反式-7,8-二羟基-7,8-二氢苯并(a)芘[(+)-和(-)-BP 7,8-二氢二醇]进行致癌性测试。这些动物在17周龄时被处死。对照小鼠每只小鼠有0.10个肺腺瘤,而用(+)-BP 7,8-二氢二醇和(-)-BP 7,8-二氢二醇处理的动物每只小鼠分别有0.16和9.28个肺腺瘤。按照上述给药方案给予高5倍的剂量时,(+)-二氢二醇每只小鼠引起2.34个肺腺瘤,(-)-BP 7,8-二氢二醇每只小鼠引起32.2个肺腺瘤。当在出生后第1、8和15天依次给予200、400和800 nmol的苯并(a)芘或(+)-BP 7,8-二氢二醇时,在小鼠17周龄时分别观察到每只小鼠有4.13和18.5个肺腺瘤。这种高剂量的(-)-BP 7,8-二氢二醇杀死了大多数小鼠。给予(-)-BP 7,8-二氢二醇导致恶性淋巴瘤高发,而(+)-BP 7,8-二氢二醇和苯并(a)芘引起恶性淋巴瘤的能力很小或没有。