Protection against malignant progression of spontaneously developing livertumors in transgenic mice expressing O-6-methylguanine-DNA methyltransferase

To study the effect of O-6-methylguanine-DNA methyltransferase (MGMT) on ca rcinogenesis, we have previously generated MGMT transgenic mice overexpress ing the bacterial MGMT gene, ada, and demonstrated that high MGMT levels in the liver suppress induction of liver tumors after treatment with an alkyl ating hepatocarcinogen, To examine the effects of life-long elevation of MG MT activity on mouse spontaneous liver tumor development, ada-transgenic an d control nontransgenic mice were compared. We also examined mutations at c odon 61 of the H-ras oncogene, reported as a hot spot in mouse liver tumors , using a direct DNA sequencing method, The results revealed no significant difference in tumor incidence or mutation spectrum, but interestingly, ada -transgenic mice were found to have fewer malignant tumors and survived lon ger, indicating a possible protective role of MGMT against malignant conver sion.