UV or X-irradiation increases the cytoplasmic accumulation of rhodamine 123 in various cancer cell lines.
OBJECTIVE
Previous studies indicated that ATP-binding cassette (ABC) membrane transporters protect against UV-induced apoptosis. We investigated the effect of UVB and X-ray irradiation on the export function of these ABC transporters in primary lymphocytes and various cancer cell lines.


METHODS
We used rhodamine accumulation assays in various human malignant cell lines and peripheral blood lymphocytes (PBL). Cells were irradiated with up to 960 mJ/cm2 and up to 50 Gy of UVB and X-ray, respectively.


RESULTS
We demonstrated that UVB as well as X-ray irradiation inhibit the export function of the ABC transporters in a dose-dependent fashion. For PBL, this effect did not correlate with an apoptotic phenotype. In the case of the tumor cell lines, even though the irradiation-induced inhibition of membrane transporters was accompanied by phosphatidylserine exposure, only a minority of cells had lost their mitochondrial membrane potential during the observation period. Furthermore, we demonstrated that the inhibition of membrane transporters is not a general feature of apoptosis.


CONCLUSIONS
Irradiation inhibits the export function of ABC transporters. Although some of the irradiated cells undergo apoptosis following irradiation, the inhibition is an unique feature accompanying irradiation and not a general hallmark of apoptotic cell death. The inhibition of drug export by irradiation may offer new potential for reverting multidrug resistance of cancer cells.
D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000528:radiation effects*; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D016923:Cell Death / Q000528:radiation effects; D002460:Cell Line; D016572:Cyclosporine / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism* / Q000528:radiation effects*; D005434:Flow Cytometry; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000528:radiation effects*; D010641:Phenotype; D011339:Probenecid / Q000494:pharmacology; D011829:Radiation Dosage; D011839:Radiation, Ionizing; D012235:Rhodamines / Q000378:metabolism*; D013442:Sulfinpyrazone / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays; D014700:Verapamil / Q000494:pharmacology; D014965:X-Rays
D018528:ATP-Binding Cassette Transporters; D012235:Rhodamines; D016572:Cyclosporine; D014700:Verapamil; D011339:Probenecid; D013442:Sulfinpyrazone