CELLULAR-RESISTANCE TO OXIDATIVE STRESS ENHANCES IN-VITRO AND IN-SITULIPOSOME-MEDIATED GENE-TRANSFER

Both H2O2-resistant fibroblast (lines OC5 and OC14) and photodynamic t herapy (PDT)-resistant fibrosarcoma (line RIF-8A) cells, known to be c ross-resistant to cisplatin, were more transfectable in vitro and in v ivo than their parental HA1 and RIF-1 cells, respectively. The transfe ction efficiencies of OC14 and the most cisplatin-resistant OC5 cells were similar, indicating that transfectability was not directly correl ated to the level of cisplatin resistance. Irt situ lipofection was mu ch greater in the cells resistant to H2O2 than to PDT. In situ CAT tra nsgene expression was significantly elevated in the cisplatin-resistan t variant 2008C13 cells grown as a subcutaneous tumor and was further increased when 2008C13 tumor-bearing SCID mice were resensitized by i.p. injection of cisplatin. These results suggest that the enhanced g ene transfer by cationic liposomes in the cells resistant to cisplatin may be, in part, due to cellular resistance to oxidative stress.