6-Thioguanine induces mitochondrial dysfunction and oxidative DNA damage in acute lymphoblastic leukemia cells. Mol Cell Proteomics 2013;12:3803–3811

Thiopurines are among the most successful chemother-apeutic agents used for treating various human diseases, including acute lymphoblastic leukemia and chronic in-flammation. Although metabolic conversion and the sub-sequent incorporation of 6-thioguanine (SG) nucleotides into nucleic acids are considered important for allowing the thiopurine drugs to induce their cytotoxic effects, alternative mechanisms may also exist. We hypothesized that an unbiased analysis of SG-induced perturbation of the entire proteome might uncover novel mechanism(s) of action of the drug. We performed a quantitative assess-ment of global protein expression in control and SG-treated Jurkat T cells by employing stable isotope labeling by amino acids in cell culture and liquid chromatography– tandem mass spectrometry (LC-MS/MS) analysis. LC