Radiation response of drug-resistant variants of a human breast cancer cell line: The effect of glutathione depletion

Journal Article · Thu Nov 01 04:00:00 EST 1990 · Radiation Research; (USA)

DOI:https://doi.org/10.2307/3577868· OSTI ID:6288738

Lehnert, S; Greene, D; Batist, G ^[1]

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1. McGill Univ., Montreal (Canada)

Two drug-resistant variants of the human breast cancer cell line MCF-7 have been shown previously to exhibit radiation resistance associated with an increase in the size of the shoulder on the radiation survival curve. In the present study, glutathione (GSH) depletion was achieved by exposure of cells to buthionine sulfoximine (BSO) with, in some cases, additional treatment with dimethyl fumarate. Levels of GSH in the adriamycin-resistant subline MCF-7 ADRR are initially lower than in the other two sublines and are depleted to a greater extent by exposure to BSO. Wild-type MCF-7 cells are not sensitized by GSH depletion when irradiated under aerated conditions but are sensitized under hypoxic conditions to an extent which is related to the level of GSH depletion. In contrast both the drug-resistant sublines (MCF-7 ADRR and the melphalan-resistant line MCF-7 MLNR) are radiosensitized by GSH depletion under both aerated and hypoxic conditions. It is hypothesized that in the case of the MCF-7 ADRR cell line, which expresses high levels of the GSH-associated redox enzyme systems, GSH-S-transferase and GSH-peroxidase (GSH-Px), radiosensitization results when GSH-Px is inhibited in GSH-depleted cells. The reasons for radiosensitization of aerated MCF-7 MLNR cells cannot be explained on this basis, however, and other factors are being examined.

• OSTI ID: 6288738
• Journal Information: Radiation Research; (USA), Journal Name: Radiation Research; (USA) Vol. 124:2; ISSN 0033-7587; ISSN RAREA
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANOXIA
ANTINEOPLASTIC DRUGS
BODY
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENZYMES
FEMALES
GLANDS
GLUTATHIONE
MAMMALS
MAMMARY GLANDS
MAN
NEOPLASMS
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
PEPTIDES
PEROXIDASES
POLYPEPTIDES
PRIMATES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY
RADIOSENSITIVITY EFFECTS
TRANSFERASES
TUMOR CELLS
VERTEBRATES
WOMEN