Gilead Sciences, Inc., USA
Research Article
Direct Measurement of the Intracellular Concentration of 8-Oxo-2'-Deoxyguanosine-5'-Triphosphate by LC-MS/MS
Author(s): Ting Wang*, Julie Farand, Karen Schwartz, Peidong Fan, Michael O. Ports, Adam Kashishian, Gregory T. Notte, Adrian S. Ray and Eisuke Murakami*
Exposure to reactive oxygen species can result in formation of oxidized nucleotides which increase the frequency of mutations, DNA damage, and cell death. MutT Homolog 1 (MTH1) is an enzyme that catalyzes removal of pyrophosphate from the highly mutagenic oxidized nucleoside triphosphate 8-oxo-2'-deoxyguanosine-5'-triphosphate (8-oxo-dGTP). Interest in MTH1 as a potential new target for cancer therapy surged due to reports of MTH1 inhibitors causing DNA damage and inducing cell death in cancer cells. However, questions have been raised about MTH1 target validation. One critical piece of information that is currently lacking is a quantitative understanding of the levels of 8-oxo-dGTP in cancer cells and the effect of MTH1 inhibition on them. In this study, we developed a sensitive and selective method to simultaneously measure the intracellular concentrations of 8-oxo guanosine nucleot.. Read More»
DOI:
10.37421/1948-593X.2020.12.237
Journal of Bioanalysis & Biomedicine received 3099 citations as per Google Scholar report