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

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/10(5) 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 (x10(6)) 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.

• Authors: D Li, W Zhang, J Zhu, P Chang, A Sahin, E Singletary, M Bondy, T Hazra, S Mitra, S S Lau, J Shen, J DiGiovanni
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 31 Issue 4 Pg. 214-23 (Aug 2001) ISSN: 0899-1987 [Print] United States
• PMID: 11536371 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2001 Wiley-Liss, Inc.

Chemical References

• 8-Hydroxy-2'-Deoxyguanosine
• Deoxyribonuclease IV (Phage T4-Induced)
• N-Glycosyl Hydrolases
• DNA-Formamidopyrimidine Glycosylase
• Carbon-Oxygen Lyases
• DNA-(Apurinic or Apyrimidinic Site) Lyase
• Deoxyguanosine

Topics

• 8-Hydroxy-2'-Deoxyguanosine
• Adult
• Breast Neoplasms (enzymology, genetics)
• Carbon-Oxygen Lyases (biosynthesis, genetics)
• DNA Damage
• DNA-(Apurinic or Apyrimidinic Site) Lyase
• DNA-Formamidopyrimidine Glycosylase
• Deoxyguanosine (analogs & derivatives, metabolism)
• Deoxyribonuclease IV (Phage T4-Induced)
• Female
• Gene Expression Regulation, Enzymologic
• Gene Expression Regulation, Neoplastic
• Humans
• N-Glycosyl Hydrolases (biosynthesis, genetics)
• Oxidative Stress
• Polymorphism, Genetic
• Polymorphism, Single-Stranded Conformational