Persistent oxidative stress in human colorectal carcinoma, but not in adenoma.
Few studies have been conducted focusing on a potential role of reactive oxygen species in tumor cell metabolism. Here we studied human colorectal adenocarcinomas and adenomas to determine whether oxidative stress is imposed on cancer cells in vivo and used specific antibodies against 8-hydroxy-2'-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (HNE)-modified proteins, and 3-nitro-L-tyrosine (3-NT) to determine whether there is an association between oxidative stress and cellular proliferation. Higher levels of oxidative modifications in DNA and proteins were observed in carcinoma cells, but not in adenoma cells, than in the corresponding nontumorous epithelial cells by immunohistochemistry as well as high-performance liquid chromatography (HPLC)-based 8-OHdG determination. The fraction of proliferating cell nuclear antigen-positive cells was proportionally associated in adenocarcinomas with the staining intensities of 8-OHdG and 3-NT. Furthermore, Western blot analysis of the proteins extracted from carcinoma cells revealed several specific proteins modified by HNE or peroxynitrite. Thus we concluded that colorectal carcinoma, but not adenoma cells, are exposed to more oxidative stress than their corresponding nontumorous epithelial cells, regardless of clinical stage and histology, and further that the oxidative stress in carcinoma cells might stimulate cellular proliferation.
Kondo
S
S
Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Japan.
Toyokuni
S
S
Iwasa
Y
Y
Tanaka
T
T
Onodera
H
H
Hiai
H
H
Imamura
M
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000230:Adenocarcinoma / Q000503:physiopathology*; D000236:Adenoma / Q000503:physiopathology*; D000328:Adult; D000368:Aged; D000447:Aldehydes / Q000737:chemistry; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000503:physiopathology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000737:chemistry; D016877:Oxidants / Q000737:chemistry; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
D000447:Aldehydes; D009566:Nitrates; D016877:Oxidants; D017382:Reactive Oxygen Species; C039642:peroxynitric acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal