Coffey R J, Meise K S, Matsui Y, Hogan B L, Dempsey P J, Halter S A
Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232.
Cancer Res. 1994 Apr 1;54(7):1678-83.
A mouse mammary tumor virus enhancer/promoter-transforming growth factor alpha transgenic mouse model has been described in which mammary tumors develop (Y. Matsui et al., Cell, 61: 1147-1155, 1990). In Line 29, spontaneous mammary tumors do not develop before 300 days of age in virgin females. Herein, Line 29 virgin females and their nontransgenic littermates have been treated with 7,12-dimethylbenzanthracene (DMBA) at varying dosages and times. Orogastric instillation of a single dose of DMBA (0.5 mg) dramatically accelerates mammary tumor formation when administered to 21- and 56-day-old virgin transgenic females compared to their nontransgenic littermates. The latency period for tumor formation is significantly shorter in transgenic mice treated with DMBA at 56 days compared to transgenic mice treated with DMBA at 21 days when results are analyzed by time from DMBA administration. To determine whether differences in the proliferative state of the mammary gland may contribute to these findings, bromodeoxyuridine incorporation was examined in the mammary glands of untreated 21- and 56-day-old mice. No differences in bromodeoxyuridine incorporation were detected between 21-day-old transgenic and nontransgenic mice. However, there was a marked increase in bromodeoxyuridine incorporation in the epithelial cells comprising the smaller ducts of 56-day-old transgenic mice compared to their nontransgenic littermates. These data indicate an enhancing interaction between a growth factor and a genotoxic carcinogen in mammary tumorigenesis and provide evidence that the transforming growth factor alpha transgene acts as a tumor promoter in this experimental model.
一种小鼠乳腺肿瘤病毒增强子/启动子-转化生长因子α转基因小鼠模型已被描述，其中会发生乳腺肿瘤（Y. Matsui等人，《细胞》，61: 1147 - 1155，1990年）。在29号线中，未交配的雌性小鼠在300日龄之前不会自发形成乳腺肿瘤。在此，对29号线未交配的雌性小鼠及其非转基因同窝小鼠在不同剂量和时间用7,12 - 二甲基苯并蒽（DMBA）进行了处理。与它们的非转基因同窝小鼠相比，对21日龄和56日龄未交配的转基因雌性小鼠经口胃内滴注单剂量的DMBA（0.5毫克）能显著加速乳腺肿瘤的形成。当从DMBA给药时间分析结果时，56日龄用DMBA处理的转基因小鼠与21日龄用DMBA处理的转基因小鼠相比，肿瘤形成的潜伏期明显更短。为了确定乳腺增殖状态的差异是否可能导致这些结果，对未处理的21日龄和56日龄小鼠的乳腺进行了溴脱氧尿苷掺入检测。在21日龄的转基因和非转基因小鼠之间未检测到溴脱氧尿苷掺入的差异。然而，与它们的非转基因同窝小鼠相比，56日龄转基因小鼠较小导管的上皮细胞中溴脱氧尿苷掺入有显著增加。这些数据表明在乳腺肿瘤发生过程中生长因子与基因毒性致癌物之间存在增强的相互作用，并提供了证据表明转化生长因子α转基因在该实验模型中起肿瘤促进剂的作用。
