Stampfer M R, Bartley J C
Proc Natl Acad Sci U S A. 1985 Apr;82(8):2394-8. doi: 10.1073/pnas.82.8.2394.
Rapidly growing primary cultures of normal human mammary epithelial cells (HMEC) were exposed to 1 microgram of benzo[a]pyrene (B[a]P) per ml for two or three 24-hr periods. The B[a]P-treated populations consistently contained cells displaying a longer period of active growth in culture compared to the untreated control cells. Widespread heterogeneity in morphology and growth patterns was evidenced in these "extended life" (EL) cultures, with multiple sequential changes in these parameters occurring during the course of their life in culture. Two apparently immortal continuous cell lines have thus far emerged from these EL cultures. These lines have been characterized to be of human mammary epithelial origin and derived from the originally treated HMEC specimen. The continuous lines do not appear to be malignantly transformed as they do not cause tumor formation in nude mice and show little or no anchorage-independent growth. Nonetheless, they have acquired several properties characteristic of tumor-derived HMEC, which distinguish them from their normal progenitors. These cell lines, as well as the EL strains, may provide useful substrates for studies to determine what agents can induce further transforming events. Additionally, analysis of the multiple steps occurring in the El cultures, as well as in the emergence of the continuous cell lines, could potentially elucidate the processes occurring during human epithelial cell carcinogenesis and escape from senescence.
将正常人乳腺上皮细胞（HMEC）的快速生长原代培养物暴露于每毫升含1微克苯并[a]芘（B[a]P）的环境中，持续两个或三个24小时周期。与未处理的对照细胞相比，经B[a]P处理的细胞群体中始终含有在培养中显示出更长活跃生长周期的细胞。在这些“延长寿命”（EL）培养物中，形态和生长模式存在广泛的异质性，在其培养过程中这些参数会发生多次连续变化。到目前为止，从这些EL培养物中已经出现了两个明显永生化的连续细胞系。这些细胞系已被鉴定为人乳腺上皮起源，且源自最初处理的HMEC标本。这些连续细胞系似乎没有发生恶性转化，因为它们在裸鼠中不会导致肿瘤形成，并且几乎没有或根本没有不依赖贴壁的生长。尽管如此，它们已经获得了一些肿瘤来源的HMEC所特有的特性，这使它们有别于其正常祖细胞。这些细胞系以及EL菌株可能为研究哪些因素能诱导进一步的转化事件提供有用的底物。此外，分析EL培养物中以及连续细胞系出现过程中发生的多个步骤，有可能阐明人类上皮细胞癌变和逃脱衰老过程中发生的机制。
