Inactivation of a tumor suppressor function in immortal Syrian hamster cells by N-methyl-N'-nitro-N-nitrosoguanidine and by 5-aza-2'-deoxycytidine.
Clonal lines of immortal Syrian hamster cells were previously isolated that either suppressed (supB+) tumorigenicity in hybrids with a malignant hamster cell line (BP6T) or had lost this suppression ability (supB-). Neither line was tumorigenic or showed anchorage-independent growth in normal growth medium. SupB- cells, but not supB+ cells, grew in agar supplemented with the growth factors EGF, PDGF and insulin (EPI), providing a selective assay for the supB- phenotype. After treatment of supB+ cells with either N-methyl-N'-nitro-N-nitrosoguanidine (10-300 ng/ml) or 5-aza-2'-deoxycytidine (25-250 ng/ml), and an expression period of 4-8 weeks, a dose-dependent increase in altered cells that grew in agar supplemented with EPI was observed. Cell lines derived from colonies in agar showed persistent EPI-stimulated growth in agar, and decreased suppression of growth in agar for hybrids with BP6T cells. Thus, carcinogen-induced loss of the tumor suppressor phenotype has been demonstrated.
West
R W
RW
Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079-9502.
Barrett
J C
JC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D006224:Cricetinae; D000077209:Decitabine; D004622:Embryo, Mammalian; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016147:Genes, Tumor Suppressor / Q000187:drug effects* / Q000502:physiology; D007328:Insulin / Q000494:pharmacology; D008647:Mesocricetus; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology
D000970:Antineoplastic Agents; D007328:Insulin; D010982:Platelet-Derived Growth Factor; D008769:Methylnitronitrosoguanidine; D004815:Epidermal Growth Factor; D000077209:Decitabine; D001374:Azacitidine