NONINVASIVE DETECTION OF ELEVATED GLUTATHIONE LEVELS IN MCF-7 CELLS RESISTANT TO 4-HYDROPEROXYCYCLOPHOSPHAMIDE

Native human mammary MCF-7 adenocarcinoma cells and a subline displayi ng resistance to 4-hydroperoxycyclophosphamide, the chemically activat ed form of cyclophosphamide, were grown as multicellular spheroids or on a collagen sponge matrix and perfused for study by P-31 and C-13 nu clear magnetic resonance spectroscopy, The natural abundance C-13 spec trum of the perfused cells exhibits well-resolved resonances due to th e intracellular glutathione (GSH). The resistant cell line shows a hig her intensity of the GSH C-13 resonances, consistent with the increase d GSB concentration determined from biochemical assays of extracts, Tr eatment of the resistant cell line with buthionine sulfoximine selecti vely diminishes the intensity of the GSH resonances in the C-13 nuclea r magnetic resonance spectrum.