HIGH-FIELD PROTON NMR INVESTIGATIONS OF THE METABOLIC PROFILES OF MULTIDRUG-SENSITIVE AND MULTID-RESISTANT LEUKEMIC-CELL LINES - EVIDENCE FOR DIMINISHED TAURINE LEVELS IN MULTIDRUG-RESISTANT CELLS

High field proton (H-1) nuclear magnetic resonance (NMR) spectroscopy has for the first time been employed to investigate and compare the me tabolic profiles of vinblastine-sensitive and -resistant T-lymphoid le ukaemic cell lines (CCRF-CEM and CEM/VLB(100) respectively) and eviden ce is presented for a significantly lower taurine content in the CEM/V LB(100) resistant subline when expressed relative to that of its drug- sensitive parental counterpart. These data suggest differences in the nature and relative involvements of taurine biosynthetic pathways betw een the two cell lines, a phenomenon that may be related to their diff ering sensitivities towards chemotherapeutic agents such as adriamycin which promote the generation of cytotoxic reactive oxygen species (RO S) in vivo. However, the H-1 H NMR data obtained provided no evidence for an increased metabolic consumption of hypotaurine (a metabolic pre cursor of taurine with powerful OH radical scavenging properties) in C CRF-CEM cells since differences observed in the hypotaurine: taurine c oncentration ratio between the drug-sensitive and -resistant cell line s were not statistically significant. Furthermore, hypotaurine is unli kely to compete with alternative endogenous OH radical scavengers pres ent such as lactate since its level in either of the two cell lines in vestigated (ca. 6.0 x 10(-8) mol./10(8) cells) is insufficient for it to act as an antioxidant in this context. The biochemical and therapeu tic significance of these results are discussed.