DNA of cancers such as renal cell carcinoma and mammary invasive ductal carcinoma, is persistently exposed to more oxidative stress than that of adjacent nornal tissue. We suggest that the concept of 'persistent oxidative stress in cancer' may open up a new research area, explaining part of the characteristic tumor biology of cancer such as activated transcription factors and proto-oncogenes, genomic instability, chemotherapyresistance, invasion and metastasis.

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An iron chelate, ferric nitrilotriacetate (Fe-NTA), Induces prox l tubular necrosis, a consequence of lipid peroxidatlon, that iall leads to a high Incidence of renal adenocarcinoma in rodents. Lipid peroidation as monitored by formation of thiobarbituric acdd-reactive suaces and bee 4-hydroxy-2-noena (HNE) was observed in the kidney homogenates of rats treated with Fe-NTA. Based on the fact that HNE is capable of reating with cellular proteins, we attempted to detect the localization of HNE-mopie proteins in rat kidney tissues with an immustochemical procedure.

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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.