Increased levels of cytosolic thioredoxin reductase activity and mRNA in rat liver nodules

Background/Aims : Thioredoxin reductase, a redox active enzyme, is induced in several tumors. This study focuses on the presence of and subcellular localisation of thioredoxin reductase in a tumor model where neoplastic lesions are selected by their resistance to the toxic effects of the promotor. Methods : Liver nodules produced by intermittent feeding of 2-acetylaminofluorene to male Wistar rats were analyzed for thioredoxin reductase (TrxR) activity and mRNA. Results : This activity was increased 3.5-fold in the cytosol but decreased 60% in the mitochondrial fraction compared to the liver of age-matched untreated animals. Only traces of activity were observed in the microsomal, plasma membrane and nuclear fractions from normal liver or nodules. The level of TrxR mRNA was 3-fold higher in nodules than in normal rat liver. Furthermore, the total level of SH groups in homogenates was 2-fold higher in the case of the nodules. Conclusions : These findings indicate that the thioredoxin system makes an important contribution to the resistant phenotype of the neoplastic liver cell, which conveys a growth advantage of significance for tumor progression.