Chemical transformation of cultured skin fibroblasts from humans genetically predisposed to cancer.
Adenomatosis of the colon and rectum (ACR) is an inherited form of cancer. Assuming that phenotypic expressions that appear in cell strains reflect its biological abnormalities, the study of cultured skin fibroblasts derived from individuals with an inherited form of cancer such as ACR provides a unique study for analysis of the oncogenic process. Growth disorders and increased susceptibility to tumor promoters and to transformation by an oncogenic RNA tumor virus have been demonstrated in these skin fibroblasts. We found that human skin fibroblasts (PF) derived from ACR individuals were sensitive to a chemical carcinogen. Cells treated only with various levels of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) underwent morphological alteration. The morphologically altered cells formed large cell aggregates when suspended in liquid growth medium above an agar base and grew to high saturation densities but did not form colonies in soft agar. Transformed cells were resistant to rechallenge of MNNG (1 microgram/ml) and showed prolonged life span compared to those untreated cells. However, no tumors were produced when cells were inoculated subcutaneously into nude mice. Data suggest that neoplastic transformation of these skin cells by chemical carcinogens is a multi-phase process.
D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000473:pathology; D005736:Gardner Syndrome / Q000473:pathology*; D006801:Humans; D008769:Methylnitronitrosoguanidine; D012867:Skin / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D008769:Methylnitronitrosoguanidine; D013755:Tetradecanoylphorbol Acetate