Establishment of "non-sepcific type isoenzyme expression rule for Phase II drug-metabolizing enzymes during chemical carcinogenesis".

点击翻译按钮获取中文摘要

Taking into consideration of the non-specific type isoenzymic characteristics of the glutathione S-transferase P-form (GST-P), which was identified by us, together with those of many other tumor marker enzymes, we tried to propose "Non-specific type isoenzyme expression rule for the Phase II drug-metabolizing enzymes during chemical carcinogenesis". This hypothesis was, however, unacceptable to some jounal submitted. Nevertheless, following results were obtained in relation to the chemical carcinogenesis.1.Broad substrate specificity and inhibitor insensitive nature, which are characteristic of the non-specific type isoenzyme, were observed for the human glutathione S-transferase P1-1(pi) as well.2.It was observed that GST substrates, such as ethacrynic acid, CDNB,and especially acrolein, were rapidly conjugated with glutathione in the presence of high GSH concentrations, suggesting that the detoxication potentials of the preneoplastic and neoplastic cells are significanly activated non-enzymatically as well.3.In relation to the gene expression of GST-P,specific antibodies to the trans-acting factors, c-JUN,c-FOS and others were prepared by immunization of rabbits and chickens with fusion proteins obtained from construction of fusion protein expressionvectors of pGEX-3X.No apparent correlation was, however, observed between the expression of the two factors and the GST-Pprotein when analyzed by the immunochemical ABC ctaining method.4.The biochemical and immunochemical properties of a total of six GST fusion proteins of oncogene products, c-JUN,c-FOS,c-MYC and c-Ha-ras and receptor proteins, GR and PPAR,were examined. It was revealed that the fusions were highly aggregative and immunogenic to rabbits and chickens.P.S., GST-P is now widely used as a specific marker in the various aspects of chemical carcinogenesis. The authors are at present interested in the physiological functions of GST-P as well as the molecular mechanism of gene expression.