High levels of γ-H2AX foci and cell membrane oxidation in adolescents with type 1 diabetes

Mutation Research
Caterina GiovanniniRoberto Scarpato

Abstract

Oxidative stress caused by an excess of free radicals is implicated in the pathogenesis and development of type 1 diabetes mellitus (T1DM) and, in turn, it can lead to genome damage, especially in the form of DNA double-strand break (DSB). The DNA DSB is a potentially carcinogenic lesion for human cells. Thus, we aimed to evaluate whether the level of oxidative stress was increased in peripheral blood lymphocytes of a group of affected adolescents. In 35 T1DM adolescents and 19 healthy controls we assessed: (1) spontaneous and H2O2-induced oxidation of cell membrane using a fluorescence lipid probe; (2) spontaneous and LPS-induced expression of iNOS protein and indirect NO determination via cytofluorimetric analysis of O2(-); (3) immunofluorescent detection of the basal level of histone H2AX phosphorylation (γ-H2AX foci), a well-validated marker of DNA DSB. In T1DM, the frequencies of oxidized cells, both spontaneous and H2O2-induced (47.13±0.02) were significantly higher than in controls (35.90±0.03). Patients showed, in general, both a reduced iNOS expression and production of NO. Furthermore, the level of spontaneous nuclear damage, quantified as γ-H2AX foci, was markedly increased in T1DM adolescents (6.15±1.08% of γ-H2AX(+...Continue Reading

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Citations

Oct 3, 2015·Biochemical and Biophysical Research Communications·Daoyin DongPeixin Yang
Apr 28, 2020·The EMBO Journal·Varun KumarPeter P Nawroth
Jul 18, 2017·Environmental and Molecular Mutagenesis·Alessia AzzaràRoberto Scarpato

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