Stabilization of membrane bound enzyme profiles by sodium selenite in N-nitrosodiethylamine induced and phenobarbital promoted hepatocarcinogenesis in rats.

ABSTRACT

As part of a substantial effort to curtail the adverse health effects posed by hepatoma, studies have been conducted to elucidate the possible mechanism for the anticarcinogenic action of sodium selenite against N-nitrosodiethylamine induced hepatocarcinogenesis. Sodium selenite administered through drinking water at a dose of 4 ppm before initiation, or during initiation and/or during the promotion period of carcinogenesis exerted an in vivo stabilizing effect on cell membranes in rat hepatoma. This was demonstrated in normal rats and in animals whose biomembranes were rendered fragile by induction of hepatoma with N-nitrosodiethylamine and subsequent treatment with sodium selenite. The obtained results have shown a significant decrease in the activities of Na(+)/K(+)-ATPases, Mg(2+)-ATPases and Ca(2+)-ATPases (P < 0.001) in erythrocyte membrane; hepatoma and surrounding liver tissue and also erythrocyte membrane are more susceptible to lysis in cancer-bearing animals. The selenite administration reversed these adverse changes to near normal in selenite-treated animals. Such stabilization of biomembranes by selenite has a beneficial effect in the treatment of hepatoma and other cancers involving abnormal fragility of cell membrane. Previous evidence from this laboratory with respect to the anticancer potency of selenite against N-nitrosodiethylamine-induced hepatoma together with the present results suggests that potentially effective therapeutic protection can be achieved by pre-supplementation of selenite.