To better understand the role of free radicals in liver carcinogenesis, endogenous antioxidant defense systems and the susceptibility of membranes to lipid peroxidation were evaluated in early lesions and in malignant tumors induced by the Solt-Farber resistant hepatocyte protocol. These parameters were also measured in the liver surrounding these tumors. In comparison with the normal liver, both nodules and carcinomas show a different biochemical pattern consisting of decreased glutathione peroxidase (GSH peroxidase) and catalase activities plus increased glutathione reductase (GSSG reductase) activity. In contrast, 1 week after the application of the initiation-selection protocol, the liver displays a high level of glutathione (GSH), high GSSG reductase activity, a reduced production of malondialdehyde and no changes in superoxide dismutase and GSH peroxidase activities. These data suggest that the liver is well protected against reactive oxygen species. During the carcinogenic process, the liver parenchyma surrounding the altered foci recovers from most of the modifications induced by the initiation-selection treatment. These results add additional support for the hypothesis that the appearance of early alterations in the liver, after a carcinogenic treatment, might be an adaptive response to a hazardous environment in which selected cell populations are transformed into nodules and/or carcinomas.

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