Overexpression of P-glycoprotein in mammalian tumor cell lines after fractionated X irradiation in vitro

• Published in: JNCI : Journal of the National Cancer Institute Vol. 82; no. 7; p. 607
• Main Authors: Hill, B T, Deuchars, K, Hosking, L K, Ling, V, Whelan, R D
• Format: Journal Article
• Language: English
• Published: United States 04-04-1990
• Subjects: Animals; Antineoplastic Agents - pharmacology; ATP Binding Cassette Transporter, Subfamily B, Member 1; Drug Resistance - genetics; Gene Expression Regulation, Neoplastic - radiation effects; Glutathione - metabolism; Glutathione Transferase - metabolism; Immunoblotting; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - genetics; Membrane Glycoproteins - radiation effects; RNA, Messenger - radiation effects; RNA, Neoplasm - radiation effects; Tumor Cells, Cultured - drug effects; Tumor Cells, Cultured - metabolism; Tumor Stem Cell Assay
• ISSN: 0027-8874
• DOI: 10.1093/jnci/82.7.607

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.