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 treated with radiotherapy. To establish a cellular model for examining this resistance phenotype a series of mammalian tumor cell lines were exposed in vitro 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 months. We now report that a comparable multidrug-resistance profile is expressed by human SK-OV-3 human ovarian tumor cells exposed in vitro to low dose (2 Gy) twice-daily fractions of X-rays given for 5 days on two consecutive weeks, essentially mimicking clinical practice, involving an overexpression of two MDR-associated proteins, P-glycoprotein and the multidrug resistance protein 1 (MRP1), with the latter being readily detectable by immunocytochemistry.
Hill
B T
BT
Division de Cancérologie, Centre de Recherche Pierre Fabre, Castres, France. bridget.hill@pierre-fabre.com
Moran
E
E
Etiévant
C
C
Perrin
D
D
Masterson
A
A
Larkin
A
A
Whelan
R D
RD
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D018432:Drug Resistance, Multiple / Q000528:radiation effects; D019008:Drug Resistance, Neoplasm / Q000528:radiation effects; D005260:Female; D019450:Genes, MDR / Q000528:radiation effects*; D006801:Humans; D008954:Models, Biological; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D017211:Treatment Failure; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D018435:ATP Binding Cassette Transporter, Subfamily B