ene Expression of Enzymes Related to Glutathione Metabolism in Anticancer Drug-resistant L1210 Sublines

Kim, Seong Yong; Kim, Jae Ryong; Kim, Jung Hye

Abstract

Glutathione(GSH) has a very important role in detoxification of cells and is closely related to antitumor drug-resistance of cancer cells. In order to evaluate the importance of glutathione metabolism in the drug-resistant cancer cells, the concentration of celluar GSH and activities of y-glutamylcysteine synthetase(GCS), y-glutamyl transpeptidase (GGT) and glutathione S-transferases(GST) in the adriamycin, vincristine, or cisplatin resistant L1210 (L1210AdR; L1210VcR, or L12100s) sublines were measured. Expression and amplification of GCS, GGT, and GST-i7 genes were also observed in the parent L1210 and the drug-resistant L1210 sublines. The concentration of GSH was increased 5.34 fold in L12100s, 2.83 fold in L1210VcR, and 1.78 fo-d in L1210AdR, compared to L1210. The activities of GCS and GGT were -increased in drug-resistant L1210 sublines. The GST activity was increased in L1210VcR and L1210Cis but decreased in L1210AdR compared to L1210. Expression of GCS, GGT, and GST-rr genes were increased in the resistant L1210 sublines compare to the parent L1210 in northern blot analyses. Overexpression of GCS, GGT, and GST-77 were observed in the resistant sublines, and the increases of the concentration of glutathione and the activities of GCS and GGT in the resistant sublines may be involved in a part of the drug-resistance in the resistant sublines.