Increased levels of cytosolic thioredoxin reductase activity and mRNA in rat liver nodules.
OBJECTIVE
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.
Björkhem
L
L
Department of Microbiology, Pathology and Immunology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden. mikael.bjornstedt@impi.ki.se
Teclebrhan
H
H
Kesen
E
E
Olsson
J M
JM
Eriksson
L C
LC
Björnstedt
M
M
D015073:2-Acetylaminofluorene / Q000633:toxicity; D000818:Animals; D003600:Cytosol / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013347:Subcellular Fractions / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics* / Q000378:metabolism*
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D015073:2-Acetylaminofluorene; D013880:Thioredoxin-Disulfide Reductase