TY - JOUR
T1 - Oxidative DNA damage and 8-hydroxy-2-deoxyguanosine DNA glycosylase/apurinic lyase in human breast cancer
AU - Li, Donghui
AU - Zhang, Weiqing
AU - Zhu, Jijiang
AU - Chang, Ping
AU - Sahin, Aysegul
AU - Singletary, Eva
AU - Bondy, Melissa
AU - Hazra, Tapas
AU - Mitra, Sankar
AU - Lau, Serrine S.
AU - Shen, Jianjun
AU - DiGiovanni, John
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - 8-hydroxy-2-deoxyguanosine
KW - 8-hydroxy-2-deoxyguanosine DNA glycosylase/apurinic lyase
KW - Breast tissue
UR - http://www.scopus.com/inward/record.url?scp=0034846112&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034846112&partnerID=8YFLogxK
U2 - 10.1002/mc.1056
DO - 10.1002/mc.1056
M3 - Article
C2 - 11536371
AN - SCOPUS:0034846112
SN - 0899-1987
VL - 31
SP - 214
EP - 223
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
IS - 4
ER -