Tumorigenic activity of benzo(e)pyrene derivatives on mouse skin and in newborn mice.
Tumorigenic activity of benzo(e)pyrene derivatives on mouse skin and in newborn mice.
复制标题
苯并（e）芘衍生物对小鼠皮肤和新生小鼠的致瘤活性。
作者：
Mildred;K. Buening;Wayne;Levin;Alexander;W. Wood;Richard;L. Chang;Roland;E. Lehr;Charles;W.;Taylor;H. Yagi;D. Jerina;Allan H. Conney
在两种小鼠肿瘤模型中测定了苯并(e)芘及其衍生物的致瘤活性。新生Swiss-Webster小鼠分别于出生后第1天、第8天和第15天腹腔注射0.4、0.8和1.6 μ mol化合物。当老鼠长到62至66周大时，实验以杀死动物的方式终止。苯并(e)芘、反式4,5-二羟基-4,5-二氢苯并(e)芘和反式9,10-二羟基-9,10-二氢苯并(e)芘在肺组织中几乎没有致瘤活性，尽管反式9,10-二羟基-9,10-二氢苯并(e)芘确实诱导了大量的肝脏肿瘤。测定了苯并芘及其衍生物在雌性CD-1小鼠皮肤上的致瘤活性。单次局部应用1.0 - 6.0 μ mol的试验化合物，7天后，每周两次应用肿瘤促进剂12- o - tetradecanoylphorol -13-acetate，持续35周。对照小鼠和经6.0 μ mol苯并(e)芘、反式4,5-二羟基-4,5-二氢苯(e)芘、反式9,10-二羟基-9,10-二氢苯(e)芘、反式9,10-二羟基-9,10,11,12-四氢苯(e)芘处理的小鼠肿瘤发生率均小于20%，乳头瘤数小于或等于0.25个/只。9,10-二氢苯并(e)芘是唯一在小鼠皮肤上具有显著肿瘤启动活性的衍生物；起始剂量为2.5 μ mol时，肿瘤发生率为67%，每只小鼠有1.43个乳头瘤。
The tumorigenic activities of benzo(e)pyrene and several of its derivatives were determined in two mouse tumor models. Newborn Swiss-Webster mice were given i.p. injections of 0.4, 0.8, and 1.6 mumol of compound on the first, eighth, and 15th day of life, respectively. When the mice were 62 to 66 weeks old, the experiment was terminated by killing the animals. Benzo(e)pyrene, trans-4,5-dihydroxy-4,5-dihydrobenzo(e)pyrene, and trans-9,10-dihydroxy-9,10-dihydrobenzo(e)pyrene had little or no tumorigenic activity in lung tissue, although trans-9,10-dihydroxy-9,10-dihydrobenzo(e) pyrene did induce a significant number of hepatic tumors. The tumor-initiating activities of benzo(e)pyrene and several of its derivatives were determined on the skin of female CD-1 mice. A single topical application of 1.0 to 6.0 mumol of the test compound was followed 7 days later by twice-weekly applications of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate for 35 weeks. Control mice and mice treated with 6.0 mumol of benzo(e)pyrene, trans-4,5-dihydroxy-4,5-dihydrobenzo(e)pyrene, trans 9,10-dihydroxy-9,10-dihydrobenzo(e)pyrene, and trans-9,10-dihydroxy-9,10,11,12-tetrahydrobenzo(e)pyrene had a tumor incidence of less than 20% and had less than or equal to 0.25 papillomas/mouse. 9,10-Dihydrobenzo(e)pyrene was the only derivative tested that had significant tumor-initiating activity on mouse skin; an initiating dose of 2.5 mumol gave a 67% tumor incidence and 1.43 papillomas/mouse.