CHARACTERIZATION OF THE P-GLYCOPROTEIN OVER-EXPRESSING DRUG-RESISTANCE PHENOTYPE EXHIBITED BY CHINESE-HAMSTER OVARY CELLS FOLLOWING THEIR INVITRO EXPOSURE TO FRACTIONATED X-IRRADIATION

Exposure of the Chinese hamster ovarian AuxB1 cell line in vitro to fr actionated X-irradiation generated sublines designated DXR-10, which p roved resistant to multiple drugs and overexpressed P-glycoprotein (Pg p), as judged by Western blotting using the C219 monoclonal antibody [ 1]. Further characterization of these irradiated DXR-10 sublines has p rovided evidence for: (i) the expression of cross-resistance to gramac idin D, taxol, puromycin and Navelbine, but not to daunomycin or mitox antrone; (ii) overexpression of the class I Pgp, as judged by Western blotting using the C494 monoclonal antibody; (iii) decreased accumulat ion of H-3-vincristine, which could be enhanced by verapamil addition; (iv) unaltered accumulation and subcellular distribution of adriamyci n; (v) significantly increased rhodamine 123 accumulation in the prese nce of verapamil; (vi) plasma-membrane ultrastructural modifications r esulting in a significantly increased surface area; (vii) numerous clo nal karyotypic alterations, with abnormalities involving the long arm of chromosome 1 being consistently identified; (viii) a lack of overex pression of sorcin; (ix) increased total glutathione levels and overex pression of glutathione S-transferase pi. The fact that only certain o f these features are considered characteristic of the 'classic' multid rug-resistant CH(R)C5 cell line supports our earlier proposal that exp osure to fractionated X-irradiation results in the expression of a uni que drug-resistance phenotype.