Oxidative DNA damage in peripheral leukocytes and its association with expression and polymorphisms of hOGG1: a study of adolescents in a high risk region for hepatocellular carcinoma in China

World J Gastroenterol. 2003 Oct;9(10):2186-93. doi: 10.3748/wjg.v9.i10.2186.

Abstract

Aim: To study the oxidative DNA damage to adolescents of hepatocellular carcinoma (HCC) families in Guangxi Zhuang Autonomous Region, China.

Methods: Peripheral leukocytes' DNA 7, 8-dihydro-8-oxoguanine (8-oxoG) and repair enzyme hOGG1 were quantified by flow-cytometry. hOGG1-Cys326Ser single nucleotide polymorphism (SNP) was distinguished by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) assay.

Results: There was a positive correlation between 8-oxoG and repair enzyme hOGG1 expression (P<0.001). HCC children (n=21) in Fusui county had a higher level of hOGG1 (P<0.01) and a lower level of 8-oxoG (P<0.05) than the controls (n=63) in Nanning city. Children in Nanning exposed to passive-smoking had a higher hOGG1 expression (P<0.05) than the non-exposers. 8-oxoG and hOGG1 were negatively correlated with body mass index, while hOGG1 was positively correlated with age. There was a peak of 8-oxoG level nearby the 12 year point. Individuals with the hOGG1 326Ser allele had a significantly marginal higher concentration of leukocyte 8-oxoG level than hOGG1 326Cys allele.

Conclusion: This is the first report using flow-cytometry to simultaneously quantify both the DNA oxidative damage and its repairing enzyme hOGG1. The results provide new insights towards a better understanding of the mechanisms of oxidative stress in a population highly susceptible to hepatocarcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Biomarkers
  • Body Mass Index
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / metabolism*
  • China / epidemiology
  • DNA Damage / immunology*
  • DNA Glycosylases / genetics*
  • DNA Glycosylases / metabolism*
  • Female
  • Flow Cytometry / methods
  • Genotype
  • Guanine / analogs & derivatives*
  • Guanine / metabolism
  • Humans
  • Leukocytes / metabolism*
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Male
  • Multivariate Analysis
  • Oxidative Stress
  • Polymorphism, Single Nucleotide
  • Risk Factors

Substances

  • Biomarkers
  • 8-hydroxyguanine
  • Guanine
  • DNA Glycosylases
  • oxoguanine glycosylase 1, human