Methylglyoxal (MG) is an endogenous mutagen, formed nonenzymatically from triose phosphates during glycolysis in eukaryotic cells. MG reacts with amino groups in proteins and DNA, forming advanced glycation end-products (AGE). The major MG-derived AGE of DNA is N2-(1-carboxyethyl)-2??-deoxyguanosine (CEdG). CEdG is much more likely than dG to form non-Watson Crick base pairs, leading to elevated mutation and cancer. The biochemistry of MG-induced DNA damage, as well as the relevant repair pathway, is currently not well understood. In this project, the effect of nucleotide excision repair (NER) on MG-induced mutation is assessed using a forward mutation assay. NER-deficient (XP-G) and NER-proficient cells (XP-G+) were transfected with MG-treated pSP189 shuttle vector; mutation frequencies were determined in the supF target gene. Treatment of DNA with 12mM of MG results in a 4-fold induction of mutation in XPG cells. This frequency is minimized in the XPG+ cells, suggesting a role of NER in the repair of MG-induced mutations.