Fibroblasts from Humans Genetically Predisposed to Colon Cancer Are Abnormally Resistant to Vitamin A

Abstract

We report here than skin fibroblasts (SF) from patients with hereditary adenomatosis of the colon and rectum (ACR) and its Gardner syndrome (GS) variant are abnormally resistant to retinoic acid (RA). The effects by RA on the proliferation of SF was concentration dependent, exhibiting a bimodal dose-response pattern that consisted of both a stimulatory and an inhibitory component. Cell density appears to modulate both the stimulatory and inhibitory effects of RA. ACR cells were abnormally resistant to RA at all concentrations tested. Although more resistant to RA-induced cytotoxicity, ACR cells showed morphological changes on exposure to RA similar to those seen in normal cells. These differential effects by RA will be used to further identify individuals at risk of this dominant form of colon cancer.