Kaighn M E, Gabrielson E W, Iman D S, Pauls E A, Harris C C
Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892.
Cancer Res. 1990 Mar 15;50(6):1890-6.
Hybrid cell lines between HuT292-DM, a human lung carcinoma line resistant to 6-thioguanine and ouabain, and either normal human bronchial epithelial cells (NHBE) or an SV40 "immortalized" but nontumorigenic derivative thereof (BEAS-2B), have been isolated by double selection. Hybrids of NHBE and HuT292-DM cells senesced after 40-43 population doublings in culture. In contrast, hybrids of BEAS-2B and HuT292-DM showed no sign of a culture "crisis" and have an indefinite life span. HuT292-DM cells produced tumors in 100% of athymic nude mice with a mean latency of 27 days, whereas tumorigenicity was totally suppressed in 76% of the BEAS-2B x HuT292-DM hybrids, with a 2- to 3-fold increased tumor latency in the remaining 24% of these hybrids. While the hybrids are hypotriploid to hypotetraploid, the parental lines are hypodiploid. The growth of HuT292-DM cells is stimulated, whereas NHBE and BEAS-2B cells are inhibited by serum. The growth response of the BEAS-2B x HuT292-DM hybrids to serum is similar to that of HuT292-DM cells. Thus, tumorigenicity and culture longevity are dominantly controlled by the nontumorigenic parent (NHBE or BEAS-2B). On the other hand, serum responsiveness is more similar to that of the tumorigenic parent (HuT292-DM).
通过双重筛选，已分离出HuT292-DM（一种对6-硫鸟嘌呤和哇巴因耐药的人肺癌细胞系）与正常人支气管上皮细胞（NHBE）或其SV40“永生化”但无致瘤性的衍生物（BEAS-2B）之间的杂交细胞系。NHBE和HuT292-DM细胞的杂交体在培养中经过40-43次群体倍增后衰老。相比之下，BEAS-2B和HuT292-DM的杂交体没有显示出培养“危机”的迹象，并且具有无限的寿命。HuT292-DM细胞在100%的无胸腺裸鼠中产生肿瘤，平均潜伏期为27天，而在76%的BEAS-2B×HuT292-DM杂交体中致瘤性被完全抑制，其余24%的这些杂交体的肿瘤潜伏期增加了2至3倍。虽然杂交体是亚三倍体至亚四倍体，但亲代细胞系是亚二倍体。HuT292-DM细胞的生长受到刺激，而NHBE和BEAS-2B细胞则受到血清抑制。BEAS-2B×HuT292-DM杂交体对血清的生长反应与HuT292-DM细胞相似。因此，致瘤性和培养寿命主要由无致瘤性的亲代（NHBE或BEAS-2B）控制。另一方面，血清反应性更类似于致瘤性亲代（HuT292-DM）。
