NEOPLASTIC TRANSFORMATION AND DNA DAMAGE OF MOUSE MAMMARY EPITHELIAL-CELLS BY N-METHYL-N'-NITROSOUREA IN ORGAN-CULTURE
NEOPLASTIC TRANSFORMATION AND DNA DAMAGE OF MOUSE MAMMARY EPITHELIAL-CELLS BY N-METHYL-N'-NITROSOUREA IN ORGAN-CULTURE
复制标题
DOI：
10.1016/0304-3835(90)90062-3
复制
发表时间：
1990-11-19
期刊：
影响因子：
9.7
通讯作者：
BANERJEE, MR
中科院分区：
文献类型：
--
作者：
DELP, CR;TREVES, JS;BANERJEE, MR
采用合适的体外培养系统，研究了一种直接致癌物对体外全乳腺器官培养中乳腺上皮细胞转化的影响。研究了n -甲基-n " -亚硝基脲（MNU）转化乳腺细胞的能力。在培养的不同时期，用单剂量或多剂量的MNU处理小鼠乳腺。为了检测MNU对乳腺细胞的肿瘤转化潜能，我们将乳腺分离，并将细胞注射到同基因雌性宿主小鼠腹股沟无软组织乳腺脂肪垫中。3-4个月后，23%的小鼠注射腺体可触及肿瘤，另有31%的小鼠出现连续移植增生肺泡结节（HANs）。组织病理检查显示肿瘤为乳腺腺癌。所有的肿瘤和增生都被二次移植到同基因动物体内，得到了组织病理学相似的肿瘤和增生。此外，利用新的缺口翻译实验也可以测量MNU对器官培养上皮细胞的DNA损伤。在乳腺培养期的第4天和第5天，腺体发生最广泛的DNA损伤。这些结果表明，小鼠乳腺上皮细胞易受直接作用致癌物MNU的致癌作用，整个乳腺培养系统为研究MNU诱导的致癌机制提供了合适的体外模型。
An appropriate in vitro system was used to study the effect of a direct-acting carcinogen on the transformation of mammary epithelial cells in the organ culture of the whole mammary gland in vitro. Studies were done to determine the ability of N-methyl-N''-nitrosourea (MNU) to transform the mammary cells in organ culture. Mouse mammary glands were treated with single or multiple doses of MNU during various periods of the culture. To assay for neoplastic transformation potential of MNU on mammary cells, mammary glands were dissociated and the cells were injected into the parenchyma-free inguinal mammary fat pad of syngeneic virgin female host mice. Palpable tumors were observed in injected glands of 23% of the mice after 3-4 months and an additional 31% showed serially transplantable hyperplastic alveolar nodules (HANs). Histopathologic examination of the tissues showed that the tumors were mammary adenocarcinoma. All tumors and hyperplasias were secondarily transplanted into syngeneic animals, resulting in tumors and hyperplasias of similar histopathology. In addition, DNA damage of the epithelial cells in organ culture caused by MNU was also measurable using the new nick translation assay. The most extensive DNA damage occurred when the glands were treated on day 4 and day 5 of the mammogenic culture period. These results demonstrate that the mouse mammary epithelial cells are susceptible to the carcinogenic action of the direct-acting carcinogen MNU and that the whole mammary gland culture system offers an appropriate in vitro model for studying the mechanism of carcinogenesis induced by MNU.