CONFERRING DRUG-RESISTANCE BY MDR1 GENE TRANSFECTION INCREASES SUSCEPTIBILITY TO IRRADIATION AND LIPID-PEROXIDATION IN 3T3 CELL-LINE

This study was performed to test the hypothesis that conferring multip le drug resistance reduces cell susceptibility to irradiation and iron -stimulated lipid peroxidation. Multidrug resistant (PN1A) and parenta l drug sensitive (PSI-2) cell lines were exposed to ADP-Fe or Ascorbat e-Fe complexes at 37 degrees C and to irradiation. Lipid peroxidation was estimated by the TEA test, whereas x-ray effect was estimated by c lonogenic assay. Cell glutathione-S-transferase (GST), total and Se-de pendent glutathione peroxidase (GSH-Px) activities, and glutathione an d vitamin E were measured. PN1A produced more peroxides than PSI-2 aft er exposure to iron complexes and formed fewer colonies after irradiat ion. Higher activities of GST and total and Se-GSH-Px were observed in PN1A. Vitamin E and total glutathione did not differ in the two cell subclones. These data show that the induction of the mdr1 phenotype by transfection of mdr1 gene in 3T3 cells increases susceptibility to ir radiation and iron stimulated lipid peroxidation.