EFFECTS OF 12-O-TETRADECANOYLPHORBOL-13-ACETATE ON FIBROBLASTS FROM INDIVIDUALS GENETICALLY PREDISPOSED TO CANCER

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (9) , 3870-3879
Abstract
Whether skin fibroblasts from individuals, with an inherited predisposition to cancer or with genetic disorders usually associated with a high risk of cancer, can be oncogenically transformed in vitro by a tumor promoter alone, was investigated. The effects of chronic and limited applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) on several properties that are associated with transformation were examined using skin fibroblasts from individuals with polyposis coli, a familial cancer syndrome, xeroderma pigmentosum, Fanconi''s anemia, and trisomy 21. TPA treatment induces similar changes on cellular morphology, growth rate, saturation density, epidermal growth factor binding, and cytoskeleton in fibroblasts from both normal and genetically predisposed individuals. None of these cell lines, however, acquired anchorage-independent growth or unlimited growth potential in culture after chronic application of TPA. Skin fibroblasts from individuals with a genetic predisposition to or a high risk of cancer may not exist in a preneoplastic or initiated state susceptible to oncogenic transformation by TPA alone. The mechanism of genetically determined cancer induction may be different from that of chemical carcinogenesis.