The use of a tumor promoter for the detection of individuals with the Gardner syndrome.
The effects of the tumor promoter 12-O-tetradecnoyl phorbol-13-acetate (TPA) on the proliferation out of cultured skin fibroblasts (SF) obtained from 21 individuals representing a single pedigree of the Gardner variant of hereditary adenomatosis of the colon and rectum (ACR) were analyzed. SF from both gene-carriers and normal individuals displayed an unusual biphasic dose-response (concaved upward), but the latter were considerably more sensitive to the toxic effects of this probe at all concentrations tested. Based on the differential sensitivity to TPA (range, 0-100 ng/ml), a good correlation has been found in this study between the results, the pedigree analysis, and the clinical findings. Of 21 individuals examined, two were apparently false-negatives. Two other individuals who are currently listed as clinically asymptomatic and, who through pedigree analysis might presumably be disease-free, appeared strongly positive by the criteria. The results extend the previous observations that the measurement of cloning efficiency in the presence of a TPA probe provides a reliable assay to distinguish SF of colorectal cancer-prone persons from those of normal subjects within a single pedigree of the Gardner syndrome.
D000293:Adolescent; D000328:Adult; D000368:Aged; D002273:Carcinogens / Q000494:pharmacology*; D002478:Cells, Cultured; D002648:Child; D002999:Clone Cells / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005188:False Negative Reactions; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D005736:Gardner Syndrome / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010704:Phorbols / Q000494:pharmacology*; D012867:Skin; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D002273:Carcinogens; D010704:Phorbols; D013755:Tetradecanoylphorbol Acetate