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

Background/Aims: Thioredoxin reductase, a redox active enzyme, is induced i n several tumors. This study focuses on the presence of and subcellular loc alisation of thioredoxin reductase in a tumor model where neoplastic lesion s are selected by their resistance to the toxic effects of the promotor. Methods: Liver nodules produced by intermittent feeding of 2-acetylaminoflu orene to male Wistar rats were analyzed for thioredoxin reductase (TrxR) ac tivity 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 untr eated animals. Only traces of activity were observed in the microsomal, pla sma membrane and nuclear fractions from normal liver or nodules. The level of TrxR mRNA was Mold higher in nodules than in normal rat liver. Furthermo re, the total level of SH groups in homogenates was 2-fold higher in the ca se of the nodules. Conclusions: These findings indicate that the thioredoxin system makes an i mportant contribution to the resistant phenotype of the neoplastic liver ce ll, which conveys a growth advantage of significance for tumor progression. (C) 2001 European Association for the Study of the Liver. Published by Els evier Science B.V. All rights reserved.