Fibroblasts from persons predisposed to cancer are abnormally resistant to 5-azacytidine-induced cytotoxicity

We have determined the sensitivity to 5-azacytidine of cultured fibroblasts obtained from clinically defined areas on the skin of patients with hereditary adenomatosis of the colon and rectum (ACR) and von Recklinghausen neurofibromatosis (NF). Fibroblasts from normal appearing skin of both ACR and NF patients were about 2- to 3-fold more resistant to 5-azacytidine-induced cytotoxicity than were fibroblasts obtained from comparable areas of normal persons. Fibroblasts from café-au-lait lesions and from neurofibromas (NF) were increasingly more resistant to 5-azacytidine than were fibroblasts taken from normal appearing skin of the same NF patients as well as of patients from different pedigrees. The results show that fibroblasts from persons predisposed to cancer and from cancer-prone tissues in such persons are abnormally resistant to 5-azacytidine as determined by the cloning efficiency assay.