title: The NAD+precursor nicotinic acid improves genomic integrity in human peripheral blood mononuclear cells after X-irradiation.
abstract: NAD+is an essential cofactor for enzymes catalyzing redox-reactions as well as an electron carrier in energy metabolism. Aside from this, NAD+consuming enzymes like poly(ADP-ribose) polymerases and sirtuins are important regulators involved in chromatin-restructuring processes during repair and epigenetics/transcriptional adaption. In order to replenish cellular NAD+levels after cleavage, synthesis starts from precursors such as nicotinamide, nicotinamide riboside or nicotinic acid to match the need for this essential molecule. In the present study, we investigated the impact of supplementation with nicotinic acid on resting and proliferating human mononuclear blood cells with a focus on DNA damage and repair processes. We observed that nicotinic acid supplementation increased NAD+levels as well as DNA repair efficiency and enhanced genomic stability evaluated by micronucleus test after x-ray treatment. Interestingly, resting cells displayed lower basal levels of DNA breaks compared to proliferating cells, but break-induction rates were identical. Despite similar levels of p53 protein upregulation after irradiation, higher NAD+concentrations led to reduced acetylation of this protein, suggesting enhanced SIRT1 activity. Our data reveal that even in normal primary human cells cellular NAD+levels may be limiting under conditions of genotoxic stress and that boosting the NAD+system with nicotinic acid can improve genomic stability.
authors.affiliation: Molecular Toxicology Group, Department of Biology, University of Konstanz, Universitaetsstr. 10, 78457 Konstanz, Germany. Electronic address: kathrin.weidele@item.fraunhofer.de.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Weidele
authors.affiliation: Molecular Toxicology Group, Department of Biology, University of Konstanz, Universitaetsstr. 10, 78457 Konstanz, Germany. Electronic address: sascha.beneke@uni-konstanz.de.
authors.forename: Sascha
authors.initials: S
authors.lastname: Beneke
authors.affiliation: Molecular Toxicology Group, Department of Biology, University of Konstanz, Universitaetsstr. 10, 78457 Konstanz, Germany. Electronic address: alexander.buerkle@uni-konstanz.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bürkle
mesh_terms: D000107:Acetylation; D000328:Adult; D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D019587:Dietary Supplements; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000528:radiation effects; D008875:Middle Aged; D009243:NAD / Q000032:analysis / Q000378:metabolism*; D009525:Niacin / Q000378:metabolism*; D011839:Radiation, Ionizing; D037761:Sirtuins / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D055815:Young Adult
chemical_list: D016159:Tumor Suppressor Protein p53; D009243:NAD; D009525:Niacin; D004247:DNA; D037761:Sirtuins
keywords: DNA repair; Genomic stability; Human peripheral blood mononuclear cells (PBMC); Micronucleus formation; NAD(+); Nicotinic acid