Transformation studies on human fibroblasts from familial polyposis coli patients and normal donors.
Transformation experiments have been carried out on human diploid fibroblasts derived from normal individuals and those from 2 groups with dominantly inherited cancer predisposition, familial polyposis coli (FPC), and multiple endocrine neoplasia, type 2 (MEN-2). Treatment with a single or multiple doses of the carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), resulted in limited anchorage-independent (AI) growth in both normal and FPC cultures; no permanent cell lines were produced but FPC cells showed increased proliferation with low doses of the carcinogen. Carcinogen treatment followed by application of the tumour promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA), for 38 weeks was insufficient to cause full transformation in cultures derived from normal people or MEN-2 patients although AI growth was induced in all 3 cell types. Three FPC cultures exhibited an extended life span over the solvent controls. Two of these are still actively dividing and have a clonal pseudodiploid karyotype.
D011125:Adenomatous Polyposis Coli / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D007700:Kinetics; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D009377:Multiple Endocrine Neoplasia / Q000473:pathology; D009369:Neoplasms / Q000209:etiology; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D008769:Methylnitronitrosoguanidine; D013755:Tetradecanoylphorbol Acetate