論文

基本情報

氏名 河手 久弥
氏名(カナ) カワテ ヒサヤ
氏名(英語) HISAYA KAWATE
所属 中村学園大学 栄養科学部 栄養科学科
職名 教授

題名

A defect in a single allele of the Mlh1 gene causes dissociation of the killing and tumorigenic actions of an alkylating carcinogen in methyltransferase-deficient mice

単著・共著の別

共著

著者

Hisaya Kawate
Riyoko Itoh
Kunihiko Sakumi
Yusaku Nakabeppu
Teruhisa Tsuzuki
Fumio Ide
Takatoshi Ishikawa
Tetsuo Noda
Hajime Nawata
Mutsuo Sekiguchi

担当区分

概要

Mice with mutations in both alleles of the Mgmt and the Mlh1 gene, the former encoding a DNA repair methyltransferase and the latter a protein functioning at an early step of mismatch repair, are as resistant to the killing action of alkylating agents as are wild-type mice, These mice yielded a large number of tumors when exposed to alkylating carcinogens, but this characteristic was subdued since they also showed a relatively high level of spontaneous tumorigenicity, as a consequence of the defect in mismatch repair. This complexity is now resolved by introducing the Mlh1(+/-) mutation, instead of Mlh1(-/-), in these methyltransferase-deficient mice. Mgmt(-/-) Mlh1(+/-) mice, with about half the amount of MLH1 protein as Mgmt(-/-) Mlh1(+/+) mice, were resistant to the killing action of N-methyl-N-nitrosourea (MNU), up to the level of 30 mg/kg body wt. Eight weeks after exposure to this dose of MNU, 40% of MNU-treated Mgmt(-/-) Mlh1(+/-) mice had thymic lymphomas and there were no tumors in those mice not given the treatment. It seems that the cellular content of MLH1 protein is a critical factor for determining if damaged cells enter into either one of the two pathways leading to mutation induction or to apototic cell death, Loss of Mlh1 expression was frequently observed in tumors of Mgmt(-/-) Mlh1(+/-) mice and this might be related to progression of the tumors.

発表雑誌等の名称

Carcinogenesis

出版者

OXFORD UNIV PRESS

21

2

開始ページ

301

終了ページ

305

発行又は発表の年月

2000/02

査読の有無

有り

招待の有無

無し

記述言語

英語

掲載種別

研究論文(学術雑誌)

国際・国内誌

国際共著

ISSN

eISSN

DOI

10.1093/carcin/21.2.301

Cinii Articles ID

Cinii Books ID

Pubmed ID

10657972

PubMed Central 記事ID

形式

無償ダウンロード

JGlobalID

arXiv ID

ORCIDのPut Code

DBLP ID