ALTERNATIVE REGULATION BETWEEN THE Ya AND Yc SUBUNIT OF LIVER GLUTATHIONE S-TRANSFERASES IN HEPATITIS AND CANCEROUS RATS

点击翻译按钮获取中文摘要

Spontaneously hepatitis in rats are similar in certain respects to human acute hepatitis and liver cancer. The hepatitis in rats occur at the age of approximately 4 months old and most rats with severe jaundice were died within one week. It was known that the hepatitis was identified as a recessive mutation of mendelian fashion. We have postulated that the mechanism of the hepatitis in rat may be due to enzyme alterations or lack in the liver. Recently. we confirmed that the rats which were breeding for over one year had liver tumors. It is well known that glutathione S-transferases are major metabolic enzyme in liver and very good marker of hepatoma.-Namely, expression of this enzyme reflects circumstances of liver.In order to investigate the mechanism of hepatitis and then hepatoma, glutathione S-transferases were purified from hepatitis rats and normal rats by -s-hexylglutathione-linked agarose column, chromatofocusing. Seven major glutathione s-transferases were isolated. We found that glutathione S-transferase 1-1 was markedly decrease, and conversely glutathione S-transferase 2-2 was markedly increase. It is known that the genes are very similar but different genes. So it seems that the gene expression alters in hepatitis rat liver. Glutathione S-transferase 4-4 also increased.We have produced a monoclonal antibody specific for glutathione S-transferase 2-2 and rabbit anti glutathione S-transferase 4-4. We determined the enzyme localization on the liver section which had neoplastic nodules by immunohistochemical method using the antibodies. The expression of glutathione S-transferase 2-2 and 4-4 seemed to be out of the neoplastic nodules.It is obvious that the gene expression alters in hepatitis rats as compared with in normal rats. It is not clear whether such a alteration is due to a clinical phenomenon, or genetical factor. Genetic analysis is now in progress.