Noninvasive detection of elevated glutathione levels in MCF-7 cells resistant to 4-hydroperoxycyclophosphamide

Native human mammary MCF-7 adenocarcinoma cells and a subline displaying resistance to 4-hydroperoxycyclophosphamide, the chemically activated form of cyclophosphamide, were grown as multicellular spheroids or on a collagen sponge matrix and perfused for study by 31P and 13C nuclear magnetic resonance spectroscopy. The natural abundance 13C spectrum of the perfused cells exhibits well-resolved resonances due to the intracellular glutathione (GSH). The resistant cell line shows a higher intensity of the GSH 13C resonances, consistent with the increased GSH concentration determined from biochemical assays of extracts. Treatment of the resistant cell line with buthionine sulfoximine selectively diminishes the intensity of the GSH resonances in the 13C nuclear magnetic resonance spectrum.