Conferring drug resistance by MDR1 gene transfection increases susceptibility to irradiation and lipid peroxidation in 3T3 cell line

Abstract

This study was performed to test the hypothesis that conferring multiple drug resistance reduces cell susceptibility to irradiation and iron-stimulated lipid peroxidation. Multidrug resistant (PN1A) and parental drug sensitive (PSI-2) cell lines were exposed to ADP-Fe or Ascorbate-Fe complexes at 37°C and to irradiation. Lipid peroxidation was estimated by the TBA test, whereas x-ray effect was estimated by clonogenic assay. Cell glutathione-S-transferase (GST), total and Se-dependent glutathione peroxidase (GSH-Px) activities, and glutathione and vitamin E were measured. PNIA produced more peroxides than PSI-2 after exposure to iron complexes and formed fewer colonies after irradiation. Higher activities of GST and total and Se-GSH-Px were observed in PNIA. Vitamin E and total glutathione did not differ in the two cell subclones. These data show that the induction of the mdrl phenotype by transfection of mdrl gene in 3T3 cells increases susceptibility to irradiation and iron stimulated lipid peroxidation