High Field Proton NMR Investigations of the Metabolic Profiles of Multidrug-Sensitive and -Resistant Leukaemic Cell Lines: Evidence for Diminished Taurine Levels in Multidrug-Resistant Cells

Abstract

High field proton (¹H) nuclear magnetic resonance (NMR) spectroscopy has for the first time been employed to investigate and compare the metabolic profiles of vinblastine-sensitive and -resistant T-lymphoid leukaemic cell lines (CCRF-CEM and CEM/VLB₁₀₀ respectively) and evidence is presented for a significantly lower taurine content in the CEM/VLB₁₀₀ 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 between the two cell lines, a phenomenon that may be related to their differing sensitivities towards chemotherapeutic agents such as adriamycin which promote the generation of cytotoxic reactive oxygen species (ROS) in vivo. However, the ¹H NMR data obtained provided no evidence for an increased metabolic consumption of hypotaurine (a metabolic precursor of taurine with powerful ·OH radical scavenging properties) in CCRF-CEM cells since differences observed in the hypotaurine: taurine concentration ratio between the drug-sensitive and -resistant cell lines were not statistically significant. Furthermore, hypotaurine is unlikely to compete with alternative endogenous ·OH radical scavengers present such as lactate since its level in either of the two cell lines investigated (ca. 6.0 × 10⁻⁸mol./10⁸ cells) is insufficient for it to act as an antioxidant in this context. The biochemical and therapeutic significance of these results are discussed.