Wislocki P G, Juliana M M, MacDonald J S, Chou M W, Yang S K, Lu A Y
Carcinogenesis. 1981;2(6):511-4. doi: 10.1093/carcin/2.6.511.
The newborn mouse lung adenoma model has been shown to be a sensitive test for studying the tumorigenicity of bay region diol epoxides and their precursor dihydrodiols. When a total dose of 28 nmol of 7,12-dimethylbenz[a]anthracene (DMBA) or its derivatives was injected i.p. into the preweaning mice, it was found that the 3,4-dihydrodiols of both DMBA and 7-hydroxymethyl-12-methylbenz[a]anthracene caused 13.3 and 4.1 times more lung adenomas than DMBA, respectively. The mice treated with the 5,6- and 8,9-dihydrodiols of DMBA, 7-hydroxymethyl-12-methylbenz[a]anthracene and its 5,6- and 8,9- and 10,11-dihydrodiols, 7-methyl-12-hydroxymethylbenz[a]anthracene and 7,12-dihydroxymethylbenz[a]anthracene developed a level of lung adenomas/mouse less than 2-fold higher than that found in the DMSO-treated control group. Liver tumors also developed in some of the mice. The percentage of mice with liver tumors also indicated that the 3,4-dihydrodiols of both DMBA and 7-hydroxymethyl-12-methylbenz[a]anthracene were more tumorigenic than DMBA itself. These data indicate that the 3,4-dihydrodiols of both DMBA and its 7-hydroxymethyl derivative may be proximate carcinogenic metabolites of DMBA in the newborn mouse.
新生小鼠肺腺瘤模型已被证明是研究湾区二醇环氧化物及其前体二氢二醇致瘤性的敏感试验。当将28 nmol的7,12-二甲基苯并[a]蒽（DMBA）或其衍生物经腹腔注射到断奶前小鼠体内时，发现DMBA和7-羟甲基-12-甲基苯并[a]蒽的3,4-二氢二醇分别导致的肺腺瘤数量比DMBA多13.3倍和4.1倍。用DMBA的5,6-和8,9-二氢二醇、7-羟甲基-12-甲基苯并[a]蒽及其5,6-、8,9-和10,11-二氢二醇、7-甲基-12-羟甲基苯并[a]蒽和7,12-二羟甲基苯并[a]蒽处理的小鼠，其每只小鼠的肺腺瘤水平比用二甲基亚砜（DMSO）处理的对照组高不到2倍。一些小鼠还发生了肝肿瘤。发生肝肿瘤的小鼠百分比也表明，DMBA和7-羟甲基-12-甲基苯并[a]蒽的3,4-二氢二醇比DMBA本身更具致瘤性。这些数据表明，DMBA及其7-羟甲基衍生物的3,4-二氢二醇可能是新生小鼠中DMBA的直接致癌代谢物。
