Inhibitory Effect And Mechanism Of Different Level Selenium On The Hepatocacinogenesis Of Rats

In part one, the effect of sodium selenite in medium on cellular growth of cultured hepatoma cell line RH-35 and normal hepatic cell line BRL was investigated with concentration of 0.3μg/mL, 0.5μg/mL, 0.6μg/mL, 0.8μg/mL, 1.0μg/mL, 1.2μg/mL, 1.5μg/mL, 2.0μg/mL. The responses of the experimental cultured cells to the dosage and exposure time of selenium were analyzed by determining the viability of cells, the activity of cell multiplication and the cell survival curve at the exposure time of 24h, 48h, 72h and 96h. The result showed that various concentration of sodium selenite could inhibit the growth of hepatoma cells at different times, whereas different concentrations of sodium selenite have no significantly effect on normal hepatic cell. But with the increasing of exposure time, sodium selenite also could possess inhibiting effect on the normal hepatic cells.In part two, the aim is to study the inhibitory effect of different level of selenium from selenium enriched malt on hepatocarcinogenesis induced by diethylnitrosamine (DENA) in rats. 186 healthy female SD rats weighted 120-150g were randomly divided into six groups. Group Ⅰ had 30 rats, fed with diet containing 0.1 mg/kg selenium from Selenium enriched malt. Selenium content in the diet from the same source in other groups as following respectively: Group Ⅱ, 30 rats, 1.0 mg/kg; GroupⅢ, 85 rats, 0.1 mg/kg; GroupⅣ, 32 rats, 0.3 mg/kg; Group Ⅴ, 26 rats, 1.0 mg/kg; GroupⅥ, 7 rats, selenium content in feed was 0.1 mg/kg during the first 8 weeks, then was increased to 3.0 mg/kg for the next 10 weeks. Rats in group Ⅰ- Ⅱ were used as normal control. Rats in group Ⅲ-Ⅵ gave drinking water with 0.01% DENA to promote the course of cancergenesis. The experiment was lasted 18 weeks. The data showed mortality rate, inhibiting-cancer rate, bodyweight, ratio of liver/body weight, size and weight of tumors in groupⅣ-Ⅵ were better than those of group Ⅲ. Positive rate of vascular endothelial growth factor (VEGF) of group Ⅲ-Ⅵ were 73.7% , 42.9% , 45.1% and 30.6% respectively. The results indicated: with the increasing of concentrations of malt-selenium, hepatic deteriorations were inhibited or delayed. Inhibition effects of group Ⅵ were the most significant among those groups. In term of the prevention, malt-selenium with the concentration of 0.3 mg/kg in diet could achieve a preferable effect and could be recommended as a reasonable dosage according to all results in this experiment. Malt-selenium can reduce the expression of VEGF ,which could be meant decrease the course of angiogenesis and forthemore inhibition and delay of hepatocarcinogenesis. In other words, inhibition of angiogenesis and expression of VEGF associated with cancergenesis may be a novel mechanism for the anticancer activity of Se in veterinary science.