Hydrogen peroxide causes greater oxidation in cellular RNA than in DNA.
Human A549 lung epithelial cells were challenged with 18O-labeled hydrogen peroxide ([18O]-H2O2), the total RNA and DNA extracted in parallel, and analyzed for 18O-labeled 8-oxo-7,8-dihydroguanosine ([18O]-8-oxoGuo) and 8-oxo-7,8-dihydro-2'-deoxyguanosine ([18O]-8-oxodGuo) respectively, using high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-MS/MS). [18O]-H2O2 exposure resulted in dose-response formation of both [18O]-8-oxoGuo and [18O]-8-oxodGuo and 18O-labeling of guanine in RNA was 14-25 times more common than in DNA. Kinetics of formation and subsequent removal of oxidized nucleic acids adducts were also monitored up to 24 h. The A549 showed slow turnover rates of adducts in RNA and DNA giving half-lives of approximately 12.5 h for [18O]-8-oxoGuo in RNA and 20.7 h for [18O]-8-oxodGuo in DNA, respectively.
Hofer
Tim
T
Institute of Environmental Medicine, Karolinska Institute, Box 210, S-171 77 Stockholm, Sweden. thofer@ufl.edu
Badouard
Carine
C
Bajak
Edyta
E
Ravanat
Jean-Luc
JL
Mattsson
Ase
A
Cotgreave
Ian A
IA
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004247:DNA / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D012313:RNA / Q000378:metabolism*
D012313:RNA; D004247:DNA; D006861:Hydrogen Peroxide