HIGH-INCIDENCE OF NITROSAMINE-INDUCED TUMORIGENESIS IN MICE LACKING DNA-REPAIR METHYLTRANSFERASE

The enzyme O-6-methylguanine-DNA methyltransferase repairs alkylation- induced DNA damage, O-6-methylguanine and O-4-methylthymine, the forme r being formed more frequently, Previously, by means of gene targeting , we generated mice in which alleles for methyltransferase were disrup ted, We now use these mouse lines, which are totally deficient in meth yltransferase activity, to examine protective effects of the enzyme ag ainst tumor formation, In gene-targeted female mice given an i,p, inje ction of 5 mg/kg of dimethylnitrosamine, a larger number of liver and lung tumors occurred, as compared with normal female mice treated in t he same manner, In male mice given a lower dose of carcinogen, the dif ference between normal and gene-targeted mice was statistically insign ificant although more tumors did form in the gene-targeted mice, Methy ltransferase apparently afforded protection from nitrosamine-induced t umorigenesis.