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Noninvasive Detection of Elevated Glutathione Levels in MCF-7 Cells Resistant to 4-Hydroperoxycyclophosphamide¹

Department of Radiology [M. P. G., K. K. M.] and The Oncology Center [O. M. C.], The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

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.

¹ This work was supported by NIH Grants CA51229 (to M. P. G.) and CA16783 (to O. M. C.).

² To whom requests for reprints should be addressed, at Division of NMR Research, 340 Traylor Building, 720 Rutland Avenue, Baltimore, MD 21205-2196.

Received 2/16/95. Accepted 4/ 5/95.

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