Suppression of tumorigenicity of a human lung carcinoma line by nontumorigenic bronchial epithelial cells in somatic cell hybrids.
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).
Kaighn
M E
ME
Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892.
Gabrielson
E W
EW
Iman
D S
DS
Pauls
E A
EA
Harris
C C
CC
D000818:Animals; D001980:Bronchi / Q000166:cytology*; D002455:Cell Division; D002459:Cell Fusion; D002460:Cell Line; D004847:Epithelial Cells; D005819:Genetic Markers; D006801:Humans; D006822:Hybrid Cells / Q000166:cytology*; D007621:Karyotyping; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D014407:Tumor Cells, Cultured / Q000166:cytology*
D005819:Genetic Markers