Characterization of the P-glycoprotein over-expressing drug resistance phenotype exhibited by Chinese hamster ovary cells following their in-vitro exposure to fractionated X-irradiation.
Exposure of the Chinese hamster ovarian AuxB1 cell line in vitro to fractionated X-irradiation generated sublines designated DXR-10, which proved resistant to multiple drugs and overexpressed P-glycoprotein (Pgp), as judged by Western blotting using the C219 monoclonal antibody. Further characterization of these irradiated DXR-10 sublines has provided evidence for: (i) the expression of cross-resistance to gramacidin D, taxol, puromycin and Navelbine, but not to daunomycin or mitoxantrone; (ii) overexpression of the class I Pgp, as judged by Western blotting using the C494 monoclonal antibody; (iii) decreased accumulation of 3H-vincristine, which could be enhanced by verapamil addition; (iv) unaltered accumulation and subcellular distribution of adriamycin; (v) significantly increased rhodamine 123 accumulation in the presence of verapamil; (vi) plasma-membrane ultrastructural modifications resulting in a significantly increased surface area; (vii) numerous clonal karyotypic alterations, with abnormalities involving the long arm of chromosome 1 being consistently identified; (viii) a lack of overexpression of sorcin; (ix) increased total glutathione levels and overexpression of glutathione S-transferase pi. The fact that only certain of these features are considered characteristic of the 'classic' multidrug-resistant CHRC5 cell line supports our earlier proposal that exposure to fractionated X-irradiation results in the expression of a unique drug-resistance phenotype.
McClean
S
S
Cellular Chemotherapy Laboratory, Imperial Cancer Research Fund, London, UK.
Whelan
R D
RD
Hosking
L K
LK
Hodges
G M
GM
Thompson
F H
FH
Meyers
M B
MB
Schuurhuis
G J
GJ
Hill
B T
BT
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D016466:CHO Cells / Q000378:metabolism* / Q000528:radiation effects / Q000648:ultrastructure; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002871:Chromosome Banding; D006224:Cricetinae; D004347:Drug Interactions; D004351:Drug Resistance / Q000235:genetics; D005978:Glutathione / Q000378:metabolism; D007621:Karyotyping; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010641:Phenotype
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D005978:Glutathione