Oxidative stress is insignificant in N1S1-transplanted hepatoma despite markedly declined activities of the antioxidant enzymes

It has been proposed that persistent oxidative stress accounts for the incr eased levels of DNA damage in cancer tissues. We have examined the profile of anti-oxidant enzymes in a transplanted hepatic tumor model by injecting N1S1 rat hepatoma cells into the liver of Sprague-Dawley rats. The transpla nted N1S1 tumors displayed characteristics resembling human hepatocellular carcinoma. The immunoreactivities of catalase (CAT), manganese-superoxide d ismutase (Mn SOD), copper/zinc-SOD (Cu/Zn SOD), and glutathione peroxidase (GPx) were found to decrease significantly. The enzyme activity in tumors d ecreased 26.2-, 4.2-, 4.5-, and 5.4-fold for CBT, Mn SOD, Cu/Zn SOD, and GP x, respectively, relative to those in normal liver tissue from the same ani mals. In contrast, the mRNA levels of CAT and GPx in tumors decreased only 5- and 2-fold, respectively, and the mRNA levels of Cu/Zn SOD and Mn SOD sh owed either no change or an increase as compared to those of normal liver t issue. The contents of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and thiobarbit uric acid-reactive substances (TBARS) were comparable to those of normal co ntrols. Furthermore, mitochondrial production of superoxide in tumors was 4 times lower than that in normal tissues. In conclusion, the data indicate that the reduced activities of anti-oxidant enzymes in the N1S1 tumor did n ot cause significant oxidative stress.