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

Tomoo Iwakuma, Kunihiko Sakumi, Yoko Nakatsuru, Hisaya Kawate, Hisato Igarashi, Akiko Shiraishi, Teruhisa Tsuzuki, Takatoshi Ishikawa, Mutsuo Sekiguchi

Research output: Contribution to journalArticle

76 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1631-1635
Number of pages5
JournalCarcinogenesis
Volume18
Issue number8
DOIs
Publication statusPublished - Aug 1997

All Science Journal Classification (ASJC) codes

  • Cancer Research

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