Formation of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins in human renal-cell carcinoma.
To study the possible involvement of reactive oxygen species (ROS) in the tumor biology of human renal-cell carcinoma (RCC), we analyzed 35 cases of RCC for 2 parameters of oxidative damage: 8-hydroxy-2'-deoxyguanosine (8-OHdG), a mutation-prone DNA-base-modified product, was measured by means of high-performance liquid chromatography (HPLC) with an electrochemical (EC) detector, and 4-hydroxy-2-nonenal (HNE)-modified proteins were measured with a polyclonal antibody against HNE-modified proteins. A 54% higher content of 8-OHdG was found in RCC than in the corresponding non-tumorous kidney, suggesting that the DNA of RCC is more exposed to ROS than is the DNA of non-tumorous kidneys. Immunohistochemistry for HNE-modified proteins showed a distinct staining pattern of fine to coarse granularity in the cytoplasm of RCC (n = 15), implying that lipid peroxidation products are located in cytoplasmic organelles. These results suggest that RCC constitutionally elaborates more ROS than is produced by the non-tumorous parts of kidneys. No correlation was found between clinical stage, histology, age or sex and the 2 parameters examined.
Okamoto
K
K
Department of Urology, Faculty of Medicine, Kyoto University, Japan.
Toyokuni
S
S
Uchida
K
K
Ogawa
O
O
Takenewa
J
J
Kakehi
Y
Y
Kinoshita
H
H
Hattori-Nakakuki
Y
Y
Hiai
H
H
Yoshida
O
O
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000447:Aldehydes / Q000032:analysis / Q000378:metabolism*; D000906:Antibodies; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013194:Staining and Labeling / Q000379:methods
D000447:Aldehydes; D000906:Antibodies; D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal