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Oxidative DNA damage and 8‐hydroxy‐2‐deoxyguanosine DNA glycosylase/apurinic lyase in human breast cancer
Author(s) -
Li Donghui,
Zhang Weiqing,
Zhu Jijiang,
Chang Ping,
Sahin Aysegul,
Singletary Eva,
Bondy Melissa,
Hazra Tapas,
Mitra Sankar,
Lau Serrine S.,
Shen Jianjun,
DiGiovanni John
Publication year - 2001
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.1056
Subject(s) - biology , oxidative stress , microbiology and biotechnology , deoxyguanosine , breast cancer , dna glycosylase , 8 hydroxy 2' deoxyguanosine , population , dna , dna damage , cancer , endocrinology , dna oxidation , biochemistry , genetics , medicine , environmental health
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 (×10 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. © 2001 Wiley‐Liss, Inc.