The use of a tumor promoter for the detection of individuals with the gardner syndrome

Abstract

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),^1,2 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.