MGMT [MT3.1]

MGMT (O6-methylguanine-DNA methyltransferase) is transcriptionally activated in response to DNA damage and functions to repair mutagenic and cytotoxic O6-alkylguanine lesions caused by carcinogens or cytostatic drugs. MGMT induction by ionising radiation does not occur in p53-deficient mice, suggesting that MGMT induction may require p53. Similarly, MGMT mRNA and protein were shown to be inducible by ionising radiation only in cell lines that express functional p53, and not in cell lines that do not express wild type p53. In contrast, in a study of oral cancer cell lines, high MGMT activity was associated with the presence of mutant p53. Similarly, MGMT activity was significantly lower in ovarian tumors with wild-type p53 than in tumors with mutant p53, supporting the view that wild type p53 downregulates the
basal MGMT promoter.