Expression of p53 in Rat Liver During Tumor Promotion by Phenobarbita / 环境与健康杂志

ABSTRACT

Objective To investigate the effects of p53 protein and mRNA expression in rat liver tumor promotion by phenobarbital(PB). Methods Male Wistar rats were randomly divided into 6 groups,i. e. higher dose group,middle dose group,lower dose group,tumor-initiating control group,tumor-promoting group and normal control group. The rat liver tumor DEN-initiating-PB-promoting model was established among higher dose group,middle dose group,lower dose group and tumor-initiating control group. The rats in higher dose group,middle dose group and lower dose group were fed with feed containing 500,100,50 mg/kg PB respectively. The rats in liver-tumor promoting control group were only fed with normal feed. The rats in tumor-promoting group weren't initiated by DEN,were only fed with feed containing 500 mg/kg PB. The rats in normal control groups weren't treated by any factors. At the 1st,5th,10th,15th,20th,30th week of the exposure to PB,the expression of p53 protein and p53 mRNA of the rats in every group were determined by immunohistochemistry and in situ hybridization respectively. Results The expression of the mutant type p53(mtp53) protein was found in liver tumor-initiated rats which revealed precancerous lesion. The expression of p53 protein of rats increased in higher and middle dose groups,and showed higher levels in lower dose group and liver tumor-initiating control group compared with those of normal control group which didn't variate significantly with the prolongation of period of exposure to PB. The expression of wild type p53 (wtp53) mRNA showed lower levels in rats of normal control group and liver tumor-promoting group,showed higher levels in higher dose group,middle dose group,lower dose group and liver tumor-initiating control group compared with those in normal control group. The expression of wtp53 mRNA decreased in higher dose group and middle dose group,increased a little in lower dose group and liver-tumor-initiating with the prolongation of period of exposure to PB. Conclusion During the promoting stage of rat liver tumorigenesis tumor promotor PB might reduce the expression of wtp53 and induce mtp53 expression,which affected the cell cycle arrest and apoptosis,and might favor clonal expansion of preneoplastic hepatocytes,which promoted the formation of liver tumor.