Enhanced sensitivity to alkylating agent in lymphocytes from patients with multiple endocrine neoplasia type 1.
Chromosome instability is known to be associated with certain autosomal recessive 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 instability in patients with MEN 1 has been described. The clinical features of MEN 1 are, however, distinct from other DNA instability syndromes except predisposition to tumors. Therefore, we reevaluated chromosome instability in patients with familial MEN 1. An increase in the frequency of chromosome aberrations was observed in MEN 1 patients but not in control subjects when peripheral mononuclear cells were exposed to an alkylating agent, diepoxybutane (DEB). DEB reduced survival of mononuclear cells in a dose-dependent manner in both MEN 1 patients and control subjects, but this effect was more prominent in MEN I patients. There was no apparent correlation between certain MEN1 gene mutations and sensitivity to DEB. From these results, we conclude that hypersensitivity to alkylating agents exists in patients with MEN 1. Molecular mechanisms of this phenomenon and relationship to tumorigenesis in endocrine organs should be elucidated.
Itakura
Y
Y
Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine, Matsumoto, Japan.
Sakurai
A
A
Katai
M
M
Ikeo
Y
Y
Hashizume
K
K
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000187:drug effects* / Q000648:ultrastructure; D004273:DNA, Neoplasm / Q000187:drug effects; D004852:Epoxy Compounds / Q000494:pharmacology*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000648:ultrastructure; D009000:Monocytes / Q000187:drug effects / Q000648:ultrastructure; D018761:Multiple Endocrine Neoplasia Type 1 / Q000473:pathology*
D018906:Antineoplastic Agents, Alkylating; D004273:DNA, Neoplasm; D004852:Epoxy Compounds; C007366:diepoxybutane