Cyclopurine (cPu) lesions: what, how, and why?

Abstract

On May 7 2019, a “Letter to the editor” appeared in this journal by J. Cadet et al. with the title “Radiation-induced (50R)and (50S)-purine 50,8-cyclo-20-deoxyribonucleosides in human cells: a revisited analysis of HPLC-MS/MS measurements” [1]. They criticised the work published by outstanding laboratories (National Institute of Standards and Technology, USA [2], University of California Riverside, USA [3]) and my own one (Consiglio Nazionale delle Ricerche, Italy [4]), questioning the LC-MS/MS methodologies used for the detection of purine 50,8-cyclo-20-deoxynucleosides (cPu) as biomarkers of DNA oxidation reactions and published in peer-review Journals like Nature, Redox Biology, Aging Cell, Analytical Chemistry, Journal of Clinical Investigation, Oncogene, EMBO J, DNA Repair, and so on. In their letter, the “revisited analysis” did not consist of any new experimental work, but the authors gave a revisitation of the DNA damage detection, referring to their own unpublished and unsuccessful attempts made back in 2000, while trying to detect and quantify the presence of cPu lesions in DNA by LC–ESI–MS/MS, in the brain of NERknockout mice and gamma-irradiated human cells (1 kGy). Based on their apparently uniquely unsuccessful but as yet unpublished results, the authors in their review started to cast doubts on peer-reviewed work published in the last 10 years from several important laboratories around the world, and advanced the hypothesis that cPu formation can be an experimental artefact.