Mass spectrometry for the identification and quantification of new types of oxidative DNA lesions

TOXI 126

Yinsheng Wang, yinsheng.wang@ucr.edu1, Haizheng Hong, haizheng.hong@email.ucr.edu2, Huachuan Cao, huachuan@ucr.edu1, and Chunang Gu, cgu001@student.ucr.edu2. (1) Department of Chemistry, University of California at Riverside, Mail Drop 027, Riverside, CA 92521-0403, (2) Environmental Toxicology Graduate Program, University of California at Riverside, 900 University Avenue, Riverside, CA 92521
Reactive oxygen species (ROS), which can be formed from both endogenous and exogenous processes, can induce damage to DNA, which has been implicated in the pathogenesis of many human diseases including cancer and ageing. We applied mass spectrometry, together with NMR, and characterized the structures of a number of intrastrand crosslink lesions induced by reactive oxygen species. Some of these lesions could also be induced in duplex DNA by gamma irradiation or Fenton reaction. Here we will show that this type of lesion could also be induced in vivo in Hela cells upon gamma irradiation. In this respect, we employed LC-MS/MS by using stable isotope-labeled internal standards and quantified the amounts of these lesions as well as the oxidative single-base lesions. In addition, we will discuss our recent LC-MS/MS results on the in vitro replication of these lesions.