Overexpression of P-glycoprotein in mammalian tumor cell lines after fractionated X irradiation in vitro.
We observed that in vitro exposure of mammalian tumor cells to fractionated x irradiation results in the expression of drug resistance. The cause of this resistance was investigated in a series of Chinese hamster ovary cell lines that had survived exposure to multiple lethal doses of radiation. These cell lines had increased levels of P-glycoprotein (Pgp), the multidrug-resistance-associated membrane glycoprotein. Consistent with the classic multidrug resistance phenotype, they exhibited cross-resistance to multiple drugs, as well as sensitivity to reversal of vincristine resistance by verapamil. However, the cell lines showed no change in their sensitivity to x rays. Pgp overexpression occurred in these cells, despite a lack of Pgp gene amplification or of significant alteration in Pgp messenger RNA levels. Although the cause of increased Pgp levels is not yet known, these data suggest a biological basis for the clinical problem of drug resistance that can occur in previously irradiated tumors.
Hill
B T
BT
Cellular Chemotherapy Laboratory, Imperial Cancer Research Fund, London, England.
Deuchars
K
K
Hosking
L K
LK
Ling
V
V
Whelan
R D
RD
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D015151:Immunoblotting; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000528:radiation effects*; D012333:RNA, Messenger / Q000528:radiation effects; D012334:RNA, Neoplasm / Q000528:radiation effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism*; D014410:Tumor Stem Cell Assay
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D005982:Glutathione Transferase; D005978:Glutathione