High incidence of nitrosamine-induced tumorigenesis in mice lacking DNA repair methyltransferase.

Abstract:

:The enzyme O6-methylguanine-DNA methyltransferase repairs alkylation-induced DNA damage, O6-methylguanine and O4-methylthymine, the former being formed more frequently. Previously, by means of gene targeting, we generated mice in which alleles for methyltransferase were disrupted. We now use these mouse lines, which are totally deficient in methyltransferase activity, to examine protective effects of the enzyme against tumor formation. In gene-targeted female mice given an i.p. injection of 5 mg/kg of dimethylnitrosamine, a larger number of liver and lung tumors occurred, as compared with normal female mice treated in the same manner. In male mice given a lower dose of carcinogen, the difference between normal and gene-targeted mice was statistically insignificant although more tumors did form in the gene-targeted mice. Methyltransferase apparently afforded protection from nitrosamine-induced tumorigenesis.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Iwakuma T,Sakumi K,Nakatsuru Y,Kawate H,Igarashi H,Shiraishi A,Tsuzuki T,Ishikawa T,Sekiguchi M

doi

10.1093/carcin/18.8.1631

subject

Has Abstract

pub_date

1997-08-01 00:00:00

pages

1631-5

issue

8

eissn

0143-3334

issn

1460-2180

journal_volume

18

pub_type

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