title: The effect of sodium selenite on liver growth and thioredoxin reductase expression in regenerative and neoplastic liver cell proliferation.
abstract: Selenium in supra-nutritional doses is tumour-preventative in animal models and in humans. In this work, we have compared the effect of sodium selenite on tumour growth in a rat hepatocarcinogenesis model with the effect of sodium selenite on the regeneration of liver mass after partial hepatectomy. In the tumour model, 5 μg/mL sodium selenite in the drinking water reduced the rate of tumour growth for up to 12 months after initiation; the volume fraction of liver cancers was 14±4% with a mean bromodeoxyuridine-index of 19±11% in the treated rats compared to a volume fraction of 26±7% with a mean bromodeoxyuridine-index of 42±27% in the control rats. Despite its efficacy in reducing tumour growth, 5 μg/mL sodium selenite treatment did not affect the gain of liver mass or the rate of cell proliferation after partial hepatectomy. In the regenerating livers, the activity of the cytosolic selenoenzyme thioredoxin reductase (TrxR1) was briefly and transiently increased, an increase further potentiated by sodium selenite. TrxR1 was selectively over expressed in proliferating liver tumours in relation to the surrounding liver tissue in the tumour model, as shown using immunohistochemistry analyses. We suggest that sodium selenite is a suitable candidate for liver cancer prevention in patients with chronic liver diseases that are dependent on sustained liver regeneration due to its differential effects on neoplastic and regenerative cell proliferation. Furthermore, the over expression of TrxR1 in liver neoplasia can only partly be explained by increased growth.
authors.affiliation: Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, S-141 86 Stockholm, Sweden.
authors.forename: Suvd
authors.initials: S
authors.lastname: Erkhembayar
authors.forename: Annelie
authors.initials: A
authors.lastname: Mollbrink
authors.forename: Lennart C
authors.initials: LC
authors.lastname: Eriksson
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008115:Liver Regeneration / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D018038:Sodium Selenite / Q000494:pharmacology*; D054481:Thioredoxin Reductase 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D054481:Thioredoxin Reductase 1; C516126:Txnrd1 protein, rat; D018038:Sodium Selenite