Modified multiple drug resistance phenotype of Chinese hamster ovary cells selected with X-rays and vincristine versus X-rays only.
Exposure of Chinese hamster ovary (CHO) cells to fractionated X-irradiation [ten fractions of 9 Gray (Gy)] resulted in the expression of a multiple drug resistance phenotype which was distinct from that of drug-selected cells in two features: (i) resistance to vinca alkaloids and epipodophyllotoxins but sensitivity to anthracyclines was retained; (ii) overexpression of P-glycoprotein (Pgp) but regulated by post-translational stability rather than by any elevation in Pgp mRNA (Hill et al., 1990). It was also reported that when these cells (designated DXR-10) were subsequently exposed to another ten fractions of 9 Gy (20 x 9 Gy in total), no further increases in drug resistance or in the extent of Pgp expression were observed. To examine this apparent plateauing of the drug resistance phenotype following X-ray pretreatment, DXR-10 cells were instead treated with ten pulsed vincristine exposures. The resultant cell line, designated DXR-10/VCR-10, proved to be more resistant to vincristine, implying that the effect of further drug selection was additive to that of X-ray pretreatment. In addition, these cells showed resistance to doxorubicin and increased Pgp expression which was matched by a concomitant elevation in Pgp mRNA. These findings appear to confirm that Pgp expression is differentially regulated in tumour cells showing drug resistance after drug as opposed to X-ray selection.
McClean
S
S
Cellular Chemotherapy Laboratory, Imperial Cancer Research Fund, London, UK.
Hill
B T
BT
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D016466:CHO Cells / Q000187:drug effects / Q000528:radiation effects; D002352:Carrier Proteins / Q000096:biosynthesis; D002460:Cell Line; D006224:Cricetinae; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics* / Q000528:radiation effects*; D015972:Gene Expression Regulation, Neoplastic; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D012235:Rhodamines; D014750:Vincristine / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D012235:Rhodamines; D014750:Vincristine; D004317:Doxorubicin