title: Effects of endotoxin on expression of ras, p53 and bcl-2 oncoprotein in hepatocarcinogenesis induced by thioacetamide in rats.
abstract: OBJECTIVE
  To evaluate the relationship between expression of ras, p53 and bcl-2 gene products and hepatocarcinogenesis since the endotoxemia produced from lipopolysaccharide administration and/or the hypophagocytic state of splenectomy significantly accelerated hepatocarcinogenesis induced by thioacetamide.
  
  
  METHODS
  The hepatocarcinoma model was induced by 6-mo oral intake of 0.03% thioacetamide. During the hepatocarcinoma modeling process, rats were additionally treated with splenectomy and/or lipopolysaccharide administration. The techniques of flow cytometry, immunohistochemistry and immunoelectronmicroscopy were applied for quantitative analysis of the expression of oncogene proteins.
  
  
  RESULTS
  In this model system, overexpression of ras p21 protein mainly occurred in the precancerous cell population or in cells in the early stage of hepatocyte transformation. The levels of ras p21 declined when nuclear DNA aneuploidy increased. Expression of bcl-2 protein slowly and steadily rose, with more hepatocytes staying in S + G2M phases, as the hepatocarcinoma became more malignant. p53 was moderately expressed during hepatocarcinogenesis. There was no statistical correlation between endotoxemia levels and the changes in levels of ras, p53 and bcl-2 gene products.
  
  
  CONCLUSIONS
  Overexpression of oncogene ras p21 was considered likely to be a precursor of premalignant hepatocytes and possibly as responsible for the initiation of hepatocarcinogenesis. Bcl-2 protein expression is proportional to the severity of malignancy in hepatocarcinogenesis. p53 may be involved in a key pathway underlying the transformation and development processes of hepatocarcinoma. This study confirmed the hypothesis that there are multiple genes and multiple steps involved in hepatocarcinogenesis. Expression of oncogene proteins reflects the properties of the premalignant and malignant cells, but is not directly related to endotoxemia statistically.
authors.affiliation: Jin-Ming Yang, De-Wu Han, Su-Yuan Hao, Xue-Hui Ma, Yuan-Chang Zhao, The Institute of Hepatology, Shanxi Medical University, Taiyuan 030001, Shanxi Procince, China.
authors.forename: J M
authors.initials: JM
authors.lastname: Yang
authors.affiliation: Jin-Ming Yang, De-Wu Han, Su-Yuan Hao, Xue-Hui Ma, Yuan-Chang Zhao, The Institute of Hepatology, Shanxi Medical University, Taiyuan 030001, Shanxi Procince, China.
authors.forename: D W
authors.initials: DW
authors.lastname: Han
authors.affiliation: Jin-Ming Yang, De-Wu Han, Su-Yuan Hao, Xue-Hui Ma, Yuan-Chang Zhao, The Institute of Hepatology, Shanxi Medical University, Taiyuan 030001, Shanxi Procince, China.
authors.forename: Q C
authors.initials: QC
authors.lastname: Liang
authors.affiliation: Jin-Ming Yang, De-Wu Han, Su-Yuan Hao, Xue-Hui Ma, Yuan-Chang Zhao, The Institute of Hepatology, Shanxi Medical University, Taiyuan 030001, Shanxi Procince, China.
authors.forename: J L
authors.initials: JL
authors.lastname: Zhao
authors.affiliation: Jin-Ming Yang, De-Wu Han, Su-Yuan Hao, Xue-Hui Ma, Yuan-Chang Zhao, The Institute of Hepatology, Shanxi Medical University, Taiyuan 030001, Shanxi Procince, China.
authors.forename: S Y
authors.initials: SY
authors.lastname: Hao
authors.affiliation: Jin-Ming Yang, De-Wu Han, Su-Yuan Hao, Xue-Hui Ma, Yuan-Chang Zhao, The Institute of Hepatology, Shanxi Medical University, Taiyuan 030001, Shanxi Procince, China.
authors.forename: X H
authors.initials: XH
authors.lastname: Ma
authors.affiliation: Jin-Ming Yang, De-Wu Han, Su-Yuan Hao, Xue-Hui Ma, Yuan-Chang Zhao, The Institute of Hepatology, Shanxi Medical University, Taiyuan 030001, Shanxi Procince, China.
authors.forename: Y C
authors.initials: YC
authors.lastname: Zhao
keywords: Gene expression; Genes, p53; Genes, ras; Liver neoplasms; Oncogene proteins; Thioacetamide