Boylan E S, Calhoon R E
Cancer Res. 1983 Oct;43(10):4879-84.
Aspects of the development, morphology, and estrogen binding capacity of mammary tumors in rats exposed prenatally to the synthetic estrogen, diethylstilbestrol (DES), and treated postnatally with 7,12-dimethylbenz(a)anthracene (DMBA) were analyzed as part of a project aimed at understanding the effects of transplacental exposure to DES on estrogen-sensitive tissues. Pregnant Sprague-Dawley rats were given injections of DES (total dose, 1.2 micrograms) or vehicle alone on Days 15 and 18 of gestation. All female offspring were given gastric intubations of DMBA, either a single 10-mg dose on Day 50 or two doses (10 mg each) on Days 50 and 57. Among rats treated postnatally with 10 mg of DMBA, the DES-exposed group had a significantly greater incidence of palpable mammary tumors than did the vehicle-exposed controls. In addition, there was an earlier time of appearance of palpable tumors in the DES-exposed group. When the data from rats treated postnatally with two 10-mg doses of DMBA were analyzed, there were no significant differences in palpable mammary tumor incidence or tumor latency between the DES-exposed and vehicle-exposed groups. When the pathology of the mammary tumors produced in rats treated with 10 mg of DMBA was analyzed, the DES-exposed group had a significantly higher proportion of benign tumors (fibroadenoma, adenoma, lobular hyperplasia) than adenocarcinomata compared to vehicle-exposed controls. Both exposure groups had similar numbers of nonpalpable mammary lesions discovered at necropsy. Estrogen binding capacities of representative adenocarcinomata did not differ significantly between the two prenatal exposure groups treated postnatally with 10 mg of DMBA. These results demonstrate the importance of the dose of the challenge carcinogen in revealing the effects of transplacental drug exposure and may have special significance for women who were exposed to DES in utero.
作为一项旨在了解经胎盘暴露于己烯雌酚（DES）对雌激素敏感组织影响的研究项目的一部分，对产前暴露于合成雌激素己烯雌酚（DES）且产后用7,12 - 二甲基苯并(a)蒽（DMBA）处理的大鼠乳腺肿瘤的发育、形态和雌激素结合能力进行了分析。在妊娠第15天和第18天，给怀孕的斯普拉格 - 道利大鼠注射DES（总剂量1.2微克）或仅注射赋形剂。所有雌性后代在第50天接受DMBA胃插管，要么单次注射10毫克剂量，要么在第50天和第57天各注射10毫克剂量。在产后用10毫克DMBA处理的大鼠中，DES暴露组可触及乳腺肿瘤的发生率显著高于赋形剂暴露对照组。此外，DES暴露组可触及肿瘤出现的时间更早。当分析产后用两次10毫克剂量DMBA处理的大鼠数据时，DES暴露组和赋形剂暴露组在可触及乳腺肿瘤发生率或肿瘤潜伏期方面无显著差异。当分析用10毫克DMBA处理的大鼠所产生的乳腺肿瘤的病理时，与赋形剂暴露对照组相比，DES暴露组良性肿瘤（纤维腺瘤、腺瘤、小叶增生）的比例显著高于腺癌。两个暴露组在尸检时发现的不可触及乳腺病变数量相似。在产后用10毫克DMBA处理的两个产前暴露组中，代表性腺癌的雌激素结合能力无显著差异。这些结果表明了激发致癌物剂量在揭示经胎盘药物暴露影响方面的重要性，可能对子宫内暴露于DES的女性具有特殊意义。
