title: DNA deaminating ability and genotoxicity of nitric oxide and its progenitors.
abstract: Nitric oxide (NO), a multifaceted bioregulatory agent and an environmental pollutant, can also cause genomic alterations. In vitro, NO deaminated deoxynucleosides, deoxynucleotides, and intact DNA at physiological pH. That similar DNA damage can also occur in vivo was tested by treating Salmonella typhimurium strain TA1535 with three NO-releasing compounds, including nitroglycerin. All proved mutagenic. Observed DNA sequence changes were greater than 99% C----T transitions in the hisG46 (CCC) target codon, consistent with a cytosine-deamination mechanism. Because exposure to endogenously and exogenously produced NO is extensive, this mechanism may contribute to the incidence of deamination-related genetic disease and cancer.
authors.affiliation: Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, MD 21702.
authors.forename: D A
authors.initials: DA
authors.lastname: Wink
authors.forename: K S
authors.initials: KS
authors.lastname: Kasprzak
authors.forename: C M
authors.initials: CM
authors.lastname: Maragos
authors.forename: R K
authors.initials: RK
authors.lastname: Elespuru
authors.forename: M
authors.initials: M
authors.lastname: Misra
authors.forename: T M
authors.initials: TM
authors.lastname: Dunams
authors.forename: T A
authors.initials: TA
authors.lastname: Cebula
authors.forename: W H
authors.initials: WH
authors.lastname: Koch
authors.forename: A W
authors.initials: AW
authors.lastname: Andrews
authors.forename: J S
authors.initials: JS
authors.lastname: Allen
mesh_terms: D003062:Codon; D004249:DNA Damage; D004269:DNA, Bacterial / Q000737:chemistry*; D003641:Deamination; D016296:Mutagenesis; D009569:Nitric Oxide / Q000737:chemistry*; D012486:Salmonella typhimurium
chemical_list: D003062:Codon; D004269:DNA, Bacterial; D009569:Nitric Oxide