Reduced Expression Level of Mgmt mRNA and β-Catenin Gene Mutation in Rat Colon Tumors

Background: O 6 -methylguanine-DNA methyl- transferase (MGMT) is a DNA repair protein and protects DNA from the biological effects of alkylating carcinogens. The purpose of this study was to investigate the association between the mRNA expression level of the Mgmt gene and mutation of the ‚-catenin gene in rat colon tumors induced by azoxymethane (AOM) plus dextran sulfate sodium (DSS). Materials and Methods: Eleven tumor samples from rat colon treated by AOM plus DSS were examined. Mutation of the ‚-catenin gene was identified by polymerase chain reaction- single strand conformation polymorphism (PCR-SSCP) analysis. The expression level of Mgmt mRNA was determined by reverse transcription-PCR (RT-PCR). Results: Four out of five adeno-carcinoma samples bearing ‚-catenin gene mutation (5 out of 11, 45%) displayed a decrease in expression levels of Mgmt mRNA (p<0.02). Conclusion: These results suggest that the reduced expression of Mgmt mRNA and ‚-catenin gene mutation may contribute to the development of rat colon tumors. O 6 -methylguanine-DNA methyltransferase (MGMT) is one of the key enzymes that protect DNA from the biological effects of alkylating agents (1). Alkylating agents such as azoxymethane (AOM) and dimethylhydrazine (DMH) are representative carcinogens of the murine colon and cause the formation of the O 6 -methylguanine (O 6 -MeG) adduct in the DNA strand (2). Once the O 6 -MeG adduct is formed,