Radiation response of drug-resistant variants of a human breast cancer cell line

Journal Article · Thu Jun 01 04:00:00 EDT 1989 · Radiation Research; (USA)

DOI:https://doi.org/10.2307/3577414· OSTI ID:5401487

Lehnert, S; Greene, D; Batist, G ^[1]

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1. McGill Univ., Montreal, Quebec (Canada)

The radiation response of drug-resistant variants of the human tumor breast cancer cell line MCF-7 has been investigated. Two sublines, one resistant to adriamycin (ADRR) and the other to melphalan (MLNR), have been selected by exposure to stepwise increasing concentrations of the respective drugs. ADRR cells are 200-fold resistant to adriamycin and cross-resistant to a number of other drugs and are characterized by the presence of elevated levels of selenium-dependent glutathione peroxidase and glutathione-S-transferase. MLNR cells are fourfold resistant to melphalan and cross-resistant to some other drugs. The only mechanism of drug resistance established for MLNR cells to date is an enhancement of DNA excision repair processes. While the spectrum of drug resistance and the underlying mechanisms differ for the two sublines, their response to radiation is qualitatively similar. Radiation survival curves for ADRR and MLNR cells differ from that for wild-type cells in a complex manner with, for the linear-quadratic model, a decrease in the size of alpha and an increase in the size of beta. There is a concomitant decrease in the size of the alpha/beta ratio which is greater for ADRR cells than for MLNR cells. Analysis of results using the multitarget model gave values of D0 of 1.48, 1.43, and 1.67 Gy for MCF-7 cells are not a consequence of cell kinetic differences between these sublines. Results of split-dose experiments indicated that for both drug-resistant sublines the extent of sublethal damage repair reflected the width of the shoulder on the single-dose survival curve. For MCF-7 cells in the stationary phase of growth, the drug-resistant sublines did not show cross-resistance to radiation; however, delayed subculture following irradiation of stationary-phase cultures increased survival to a greater extent for ADRR and MLNR cells than for wild-type cells.

• OSTI ID: 5401487
• Journal Information: Radiation Research; (USA), Journal Name: Radiation Research; (USA) Vol. 118:3; ISSN 0033-7587; ISSN RAREA
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTINEOPLASTIC DRUGS
BIOLOGICAL VARIABILITY
BODY
CELL CYCLE
DISEASES
DRUGS
ELECTROMAGNETIC RADIATION
FRACTIONATED IRRADIATION
GAMMA RADIATION
GENETIC VARIABILITY
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IN VITRO
IONIZING RADIATIONS
IRRADIATION
MAMMALS
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ORGANS
PRIMATES
RADIATIONS
RADIOSENSITIVITY EFFECTS
SURVIVAL CURVES
TOLERANCE
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VERTEBRATES