Differences in sensitivity to UVC, UVB and UVA radiation of a multidrug-resistant cell line overexpressing P-glycoprotein

Multidrug resistance (MDR) is the phenomenon in which cultured tumor cells, selected for resistance to one chemotherapeutic agent, simultaneously acqu ire resistance to several apparently unrelated drugs, The MDR phenotype is multifactorial, The best-studied mechanism involves the expression of a mem brane protein that acts as an energy-dependent efflux pump, known as P-glyc oprotein (Pgp), capable of extruding toxic materials from the cell. In this work, resistance to UVA radiation, but not to UVC nor UVB, was observed in an MDR leukemia cell line. This cell line overexpresses Pgp, To study the role of Pgp in the resistance to UVA radiation, two MDR modulators or rever sing agents (verapamil and cyclosporin A) capable of blocking Pgp activity were used. Cell viability was assessed and the techniques of flow cytometry and fluorescence microscopy were employed to measure the extrusion of rhod amine 123 by the efflux pump. The results show that MDR modulators did not modify the resistance to UVA radiation. Furthermore, although cell viabilit y was not significantly altered, Pgp function was impaired after UVA treatm ent, suggesting that this glycoprotein may be a physical target for oxidati ve damage, and that other factors may be responsible for the UVA resistance . In agreement with this, it was found that the resistant cell line present ed a higher catalase activity than the parental (non-MDR) cell line.