title: Tumor promoter induces loss of anchorage dependence in human skin fibroblasts from individuals genetically predisposed to cancer.
abstract: To examine the role of germinal mutation in transformation by phorbol esters, we studied the induction of anchorage-independent variants of mutant human diploid fibroblasts derived from normal-appearing skin of individuals with hereditary adenomatosis of the colon and rectum (ACR). Liquid cultures were chronically exposed to 12-0-tetradecanoyl phorbol-13-acetate (TPA), then plated in agar and injected subcutaneously into athymic mice. Cultured ACR cells showed an unusual biphasic dose response to TPA. Colony-forming cells in agar were obtained at a frequency of about 5 x 10(-5). They did not, however, seem to increase in frequency during subsequent passages in liquid cultures continuously exposed to TPA. The isolated anchorage-transformed clones showed an altered clonal morphology and a considerable increase in cloning efficiency in liquid cultures and agar. The results suggest that ACR cells may be used to screen for potential tumor promoters in our environment.
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000473:pathology*; D000362:Agar; D000818:Animals; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000473:pathology; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010704:Phorbols / Q000494:pharmacology*; D012004:Rectal Neoplasms / Q000473:pathology; D012867:Skin / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D010704:Phorbols; D000362:Agar; D013755:Tetradecanoylphorbol Acetate