Superoxide Anion Radicals To Promote Rat Liver Oval Cell Proliferation And Transformation Mechanism

The hepatocellular carcinoma (HCC) plays an important part in the incidence and mortality of human malignant tumors. Much research has shown that the chemical factors are related to hepatocarcinogenesis. However the mechanisms by which the carcinogens cause the disease are unclear. It has been suggested that the Reactive Oxygen Species (ROS) might be involved in the hepatocarcinogenesis, but no irrefutable evidences, especially in the studied of the cellular and molecular level in vitro, are available to prove the view.In present, for understanding the roles and mechanisms of ROS in promoting WB cell proliferation and transformation and ROS in hepatocarcinogenesis, we have studied on: 1) The relationship between the liver premature epithelia cell (liver Over Cell, OC) and hepatocarcinogenesis, 2) the role of superoxide anion(O2_<sup>- ) generated by the interaction of xanthine(X) with xanthine oxidase (XO) in promoting the proliferation and transformation of liver OC cultured in vitro(WB cell), 3) The effects of O₂^- on the physicochemical properties of WB cell membranes and Ca++, the important cellular signal transduction factors, and 4) The expression of oncogene, c-fos and c-jun, induced by O₂^- in WB cell and the role of Ca++ signaling and protein phosphorylation in the process of the induction.Firstly, using male fisher 344 rats we project two the chemical carcinogenesis models containing 2-AAA to label liver OC or mature hepatocytes respectively with ³H-Tdr and trace whereabouts of the labeled cells by autoradiography. When the preneoplastic lesions formed in the liver of the rats, the silver grains only appeared in the preneoplastic cells once labeled oval cells rather than in those labeled mature hepatocytes. This result confirms the role of OC as the precursor of HCC in hepatocarcinogenesis.Secondly, for understanding the role and mechanisms of ROS in hepatocarcinogenesis, we studied the proliferation and transformation induced by O₂^- in WB cell cultured in vitro.Using different experimental methods that can indicate cellular proliferation, we obtained the correlative and corresponding results. When 02 of low concentration stimulate the quiescent WB cell, the ratio of 570/630 nM fluorescent absorption rise by MTT colorimetric...