Low-dose twice-daily fractionated X-irradiation of ovarian tumor cells in vitro generates drug-resistant cells overexpressing two multidrug resistance-associated proteins, P-glycoprotein and MRP1

Failure of chemotherapy is frequently observed in patients previously treat ed with radiotherapy. To establish a cellular model for examining this resi stance phenotype a series of mammalian tumor cell lines were exposed in vit ro to fractionated X-irradiation and were then shown to express resistance to multiple antitumor drugs, including vincristine, etoposide and cisplatin , In these experiments the radiation was delivered as 10 fractions of 5 Gy (dose resulting in 1 log cell kill) given intermittently over several month s. We now report that a comparable multidrug-resistance profile is expresse d by human SK-OV-3 human ovarian tumor cells exposed in vitro to low dose ( 2 Gy) twice-daily fractions of Xrays given for 5 days on two consecutive we eks, essentially mimicking clinical practice, involving an overexpression o f two Mop-associated proteins, P-glycoprotein and the multidrug resistance protein 1 (MRP1), with the latter being readily detectable by immunocytoche mistry, [(C) 2000 Lippincott Williams & Wilkins.].