Oxidative DNA damage and 8-hydroxy-2-deoxyguanosine DNA glycosylase/apurinic lyase in human breast cancer

Donghui Li, Weiqing Zhang, Jijiang Zhu, Ping Chang, Aysegul Sahin, Eva Singletary, Melissa Bondy, Tapas Hazra, Sankar Mitra, Serrine S. Lau, Jianjun Shen, John DiGiovanni

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

To test the hypothesis that oxidative stress is involved in breast cancer, we compared the levels of 8-hydroxy-2-deoxyguanosine (8-oxo-dG), an oxidized DNA base common in cells undergoing oxidative stress, in normal breast tissues from women with or without breast cancer. We found that breast cancer patients (N = 76) had a significantly higher level of 8-oxo-dG than control subjects (N = 49). The mean (±SD) values of 8-oxo-dG/105 dG, as measured by high-performance liquid chromatography electrochemical detection, were 10.7±15.5 and 6.3±6.8 for cases and controls, respectively (P= 0.035). This difference also was found by immunohistochemistry with double-fluorescence labeling and laser-scanning cytometry. The average ratios (x 106) of the signal intensity of antibody staining to that of DNA content were 3.9±7.2 and 1.1±1.4 for cases (N = 57) and controls (N = 34), respectively (P = 0.008). There was no correlation between the ages of the study subjects and the levels of 8-oxo-dG. Cases also had a significantly higher level of 8-hydroxy-2-deoxyguanosine DNA glycosylase/apurinic lyase (hOGG1) protein expression in normal breast tissues than controls (P=0.008). There was no significant correlation between hOGG1 expression and 8-oxo-dG. Polymorphism of the hOGG1 gene was very rare in this study population. The previously reported exon 1 polymorphism and two novel mutations of the hOGG1 gene were found in three of 168 cases and two of 55 controls. In conclusion, normal breast tissues from cancer patients had a significantly higher level of oxidative DNA damage. The elevated level of 8-oxo-dG in cancer patients was not related to age or to deficiency of the hOGG1 repair gene.

Original languageEnglish (US)
Pages (from-to)214-223
Number of pages10
JournalMolecular Carcinogenesis
Volume31
Issue number4
DOIs
StatePublished - 2001

Keywords

  • 8-hydroxy-2-deoxyguanosine
  • 8-hydroxy-2-deoxyguanosine DNA glycosylase/apurinic lyase
  • Breast tissue

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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