Sodium selenide toxicity is mediated by O2-dependent DNA breaks.

PloS One
Gérald PeyrochePierre Plateau

Abstract

Hydrogen selenide is a recurrent metabolite of selenium compounds. However, few experiments studied the direct link between this toxic agent and cell death. To address this question, we first screened a systematic collection of Saccharomyces cerevisiae haploid knockout strains for sensitivity to sodium selenide, a donor for hydrogen selenide (H(2)Se/HSe(-/)Se(2-)). Among the genes whose deletion caused hypersensitivity, homologous recombination and DNA damage checkpoint genes were over-represented, suggesting that DNA double-strand breaks are a dominant cause of hydrogen selenide toxicity. Consistent with this hypothesis, treatment of S. cerevisiae cells with sodium selenide triggered G2/M checkpoint activation and induced in vivo chromosome fragmentation. In vitro, sodium selenide directly induced DNA phosphodiester-bond breaks via an O(2)-dependent reaction. The reaction was inhibited by mannitol, a hydroxyl radical quencher, but not by superoxide dismutase or catalase, strongly suggesting the involvement of hydroxyl radicals and ruling out participations of superoxide anions or hydrogen peroxide. The (•)OH signature could indeed be detected by electron spin resonance upon exposure of a solution of sodium selenide to O(2). Fi...Continue Reading

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Citations

Jan 24, 2013·PloS One·Marc DauplaisPierre Plateau
Feb 5, 2013·The Journal of Antimicrobial Chemotherapy·Ute ZeidlerChristophe d'Enfert
Oct 23, 2012·IUBMB Life·Aldwin Suryo Rahmanto, Michael J Davies
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Jan 28, 2017·Bioorganic & Medicinal Chemistry Letters·Márió GajdácsEnrique Domínguez-Álvarez
Feb 13, 2017·DNA Repair·Jisha ChalisseryAhmed H Hassan
Jan 11, 2017·The Journal of Toxicological Sciences·Takao TobeHideto Jinno
Jan 3, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ah-Reum LeeKwang-Lae Hoe
Jun 3, 2017·Biomolecular Concepts·Myriam LazardPierre Plateau
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Aug 7, 2021·Nucleic Acids Research·Laurence DecourtyCosmin Saveanu

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Methods Mentioned

BETA
electrophoresis
electron spin resonance
PCR
FACS
ESR
flow cytometry

Software Mentioned

ImageJ

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