title: High level glucose increases mutagenesis in human lymphoblastoid cells.
abstract: Epidemiological data have suggested an increased cancer rates in diabetic patients, for which the underlying mechanism is poorly understood. We studied whether high level of glucose (HG) treatment that mimic the hyperglycemic condition in diabetes mellitus is mutagenic. Mutagenesis studies were carried out at both hypoxanthine phosphoribosyltransferase (hprt) and thymidine kinase (tk) loci. Role of p53 in HG-induced mutagenesis was also investigated by using human lymphoblastoid cell lines derived from same donor but differs in p53 statuses; TK6 has wild-type p53, NH32 has null p53, and WTK1 has mutant p53 (ile237). In addition, we studied the influence of antioxidant treatment on HG-induced mutagenesis. Mutation fractions at both loci increased significantly in all three lines at 21 and 28 days after HG treatments. At tk locus, the increase of a class of mutants with normal growth rate is mainly responsible for the overall increased mutant fraction. Compared to TK6 cells, both NH32 and WTK1 cells showed an early onset of mutagenesis. Treatment of cells with antioxidant N-acetyl-L-cysteine partially reduced HG induced mutagenesis. This study is the first to indicate that HG is able to induce gene mutation which may be one of the important mechanisms of diabetes-associated carcinogenesis.
authors.affiliation: Department of Environmental, Radiological Health Science, Colorado State University, Fort Collins, Colorado 80521, USA. ying.zhang@colostate.edu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Junqing
authors.initials: J
authors.lastname: Zhou
authors.forename: Tieli
authors.initials: T
authors.lastname: Wang
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
mesh_terms: D002461:Cell Line, Transformed; D016166:Free Radical Scavengers; D016158:Genes, p53; D005947:Glucose / Q000502:physiology*; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D016296:Mutagenesis / Q000502:physiology*; D013937:Thymidine Kinase / Q000235:genetics*
chemical_list: D016166:Free Radical Scavengers; D007041:Hypoxanthine Phosphoribosyltransferase; D013937:Thymidine Kinase; D005947:Glucose