title: The influence on DNA damage of glycaemic parameters, oral antidiabetic drugs and polymorphisms of genes involved in the DNA repair system.
abstract: The hyperglycaemia seen in type 2 diabetes mellitus (DM2) is associated with increased oxidative stress and production of reactive oxygen species, both of which are factors that can provoke DNA damage. Notwithstanding, other factors, including medications and individual susceptibility, can also induce this type of DNA lesion. The objective of this study was, therefore, to investigate the influence of glycaemic control, oral antidiabetic drugs (metformin and glibenclamide) and polymorphisms of the XRCC1 and XRCC3 genes on the frequency of DNA damage in DM2 patients, which was accessed by the cytokinesis-block micronucleus cytome and the comet assays on the ex vivo mitogenically stimulated lymphocytes. The 53 people recruited to take part in the study were already on treatment with metformin and were followed for 5 months. Ten of these patients were put on combined treatment with the addition of glibenclamide. It was observed that the greater the plasma metformin concentration, the lower the frequency of micronuclei (MN) in the sample total (P = 0.009) and also that the subset of patients using combined treatment including glibenclamide had a significantly higher MN rate 90 days after starting combined treatment (P = 0.024). In the subset who only took metformin, the rate of MN was significantly higher among carriers of the 399Gln allele on the XRCC1 gene (P = 0.008). In addition, homozygotes for the 241Thr allele exhibited a significant increase in MN in the combined treatment group (P = 0.008). Our results suggest that different combinations of oral antidiabetic drugs and polymorphisms on genes involved in the DNA damage repair system could influence the frequency of this type of chromosome lesion, which can be a useful biomarker for assessing the risk of developing cancer.
authors.affiliation: Health Sciences Institute, Universidade Feevale, Novo Hamburgo, Rio Grande do Sul 93352-000, Brazil.
authors.forename: Bruna Santos
authors.initials: BS
authors.lastname: da Silva
authors.forename: Diego Luiz
authors.initials: DL
authors.lastname: Rovaris
authors.forename: Rafaela Milan
authors.initials: RM
authors.lastname: Bonotto
authors.forename: Jéssica Brasil Figueiredo
authors.initials: JB
authors.lastname: Meyer
authors.forename: Ramona Elisa
authors.initials: RE
authors.lastname: Grohe
authors.forename: Magda Susana
authors.initials: MS
authors.lastname: Perassolo
authors.forename: Roberta de Passos
authors.initials: Rde P
authors.lastname: Palazzo
authors.forename: Sharbel Weidner
authors.initials: SW
authors.lastname: Maluf
authors.forename: Rafael
authors.initials: R
authors.lastname: Linden
authors.forename: Fabiana Michelsen
authors.initials: FM
authors.lastname: de Andrade
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D020552:Comet Assay; D003430:Cross-Sectional Studies; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005905:Glyburide / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use; D015162:Micronucleus Tests; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D007004:Hypoglycemic Agents; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; D008687:Metformin; D005905:Glyburide