title: Differential response of familial polyposis fibroblasts to two bifunctional alkylating agents.
abstract: Skin fibroblasts from three subjects with familial polyposis coli, a hereditary disorder predisposing to colon cancer, exhibited an unexpected insensitivity to mitomycin C (MMC). Sister chromatid exchanges (SCEs) were either reduced or unchanged after exposure to MMC, while another bi-functional alkylating agent, diepoxybutane (DEB), induced an increase in SCE level at a low, equitoxic dosage in parallel experiments. Increased sensitivity to MMC as assayed by colony formation was, however, shown by one of the subjects with polyposis. These cells with the familial polyposis genotype may have a deficiency in the DNA repair system handling MMC-induced alkylation damage yet remain capable of repairing damage induced by DEB alkylation. This deficiency may contribute to the increased frequency of neoplastic transformation known to occur in these cells in vivo.
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology*; D000478:Alkylation; D003114:Colony-Forming Units Assay; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003434:Crossing Over, Genetic / Q000187:drug effects*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007417:Intestinal Polyps / Q000235:genetics*; D009153:Mutagens / Q000494:pharmacology; D012854:Sister Chromatid Exchange / Q000187:drug effects*
chemical_list: D000477:Alkylating Agents; D003432:Cross-Linking Reagents; D009153:Mutagens