MISC

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

Separation of killing and tumorigenic effects of an alkylating agent in mice defective in two of the DNA repair genes

単著・共著の別

 

著者

H Kawate
K Sakumi
T Tsuzuki
Y Nakatsuru
T Ishikawa
S Takahashi
H Takano
T Noda
M Sekiguchi

担当区分

 

概要

Alkylation of DNA at the O-6-position of guanine is one of the most critical events leading to mutation, cancer, and cell death. The enzyme O-6-methylguanine-DNA methyltransferase repairs O-6-methylguanine as well as a minor methylated base, O-4-methylthymine, in DNA. Mouse lines deficient in the methyltransferase (MGMT) gene are hypersensitive to both the killing and to the tumorigenic effects of alkylating agents. We mow show that these dual effects of an alkylating agent can be dissociated by introduction of an additional defect in mismatch repair. Mice with mutations in both alleles of the MGMT gene and one of the mismatch repair genes, MLH1, are as resistant to methylnitrosourea (MNU) as are wild-type mice, in terms of survival, but do have numerous tumors after receiving MNU. in contrast to MGMT(-/-)MLH1(+) mice with decrease in size of the thymus and hypocellular bone marrow after MNU administration, no conspicuous change was found in MGMT(-/-)MLH1(-/-) mice treated in the same manner. Thus, killing and tumorigenic effects of an alkylating agent can be dissociated by preventing mismatch repair pathways.

発表雑誌等の名称

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

出版者

NATL ACAD SCIENCES

95

9

開始ページ

5116

終了ページ

5120

発行又は発表の年月

1998-04

査読の有無

無し

依頼の有無

無し

記述言語

英語

掲載種別

 

国際・国内誌

 

国際共著

 

ISSN

 

eISSN

 

DOI

10.1073/pnas.95.9.5116

Cinii Articles ID

 

Cinii Books ID

 

Pubmed ID

 

PubMed Central 記事ID

 

形式

無償ダウンロード

JGlobalID

 

arXiv ID

 

ORCIDのPut Code

 

DBLP ID