Enhanced sensitivity to alkylating agent in lymphocytes from patients withmultiple endocrine neoplasia type 1

Chromosome instability is known to be associated with certain autosomal rec essive cancer-prone disorders such as Fanconi's anemia. Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disorder characterized by development of tumors in two or more endocrine organs, and chromosome inst ability in patients with MEN 1 has been described. The clinical features of MEN 1 are, however, distinct from other DNA instability syndromes except p redisposition to tumors. Therefore, we reevaluated chromosome instability i n patients with familial MEN 1. An increase in the frequency of chromosome aberrations was observed in MEN I patients but not in control subjects when peripheral mononuclear cells were exposed to an alkylating agent, diepoxyb utane (DEB). DEB reduced survival of mononuclear cells in a dose-dependent manner in both MEN 1 patients and control subjects, but this effect was mor e prominent in MEN 1 patients. There was no apparent correlation between ce rtain MEN1 gene mutations and sensitivity to DEB. From these results, we co nclude that hypersensitivity to alkylating agents exists in patients with M EN1. Molecular mechanisms of this phenomenon and relationship to tumorigene sis in endocrine organs should be elucidated. (C) 2000 Editions scientifiqu es et medicales Elsevier SAS.