Livesey J C, Golden R N, Shankland E G, Grunbaum Z, Richards T L, Wade R A, Krohn K A
Department of Radiology, University of Washington, Seattle 98195.
Cancer Res. 1989 Apr 15;49(8):1937-40.
The oxidation state of tissues influences their response to cancer therapy. We have devised a novel approach to the measurement of thiol redox which is based on the relative nuclear magnetic resonance signal intensity from carbon-13 adjacent to sulfur in metabolites of the redox-sensitive phosphorothioate drug, S-2-(3-methylaminopropylamino)ethylphosphorothioic acid (WR3689). Incubation of WR3689 metabolites under oxidizing conditions results in quantifiable changes in the 13C nuclear magnetic resonance spectrum stoichiometrically related to the degree of oxidation in mouse liver homogenate in vitro. Drug oxidation is competitive with the oxidation of tissue-derived thiol groups under these conditions. Noninvasive measurement of redox state may assist in designing more effective strategies for altering normal and malignant tissue response to cancer therapy.
组织的氧化状态会影响它们对癌症治疗的反应。我们设计了一种测量硫醇氧化还原状态的新方法，该方法基于氧化还原敏感的硫代磷酸酯药物S-2-(3-甲基氨基丙基氨基)乙硫代磷酸（WR3689）代谢物中与硫相邻的碳-13的相对核磁共振信号强度。在氧化条件下孵育WR3689代谢物会导致体外小鼠肝脏匀浆中13C核磁共振谱发生可量化的变化，这些变化与氧化程度呈化学计量关系。在这些条件下，药物氧化与组织衍生硫醇基团的氧化相互竞争。氧化还原状态的非侵入性测量可能有助于设计更有效的策略，以改变正常组织和恶性组织对癌症治疗的反应。
