DNA Deaminating Ability and Genotoxicity of Nitric Oxide and its Progenitors

David A. Wink(Frederick National Laboratory for Cancer Research), Kazimierz S. Kasprzak(Frederick National Laboratory for Cancer Research), Chris M. Maragos(Frederick National Laboratory for Cancer Research), Rosalie K. Elespuru(United States Food and Drug Administration), Manoj Misra(Frederick National Laboratory for Cancer Research), Tambra M. Dunams(Frederick National Laboratory for Cancer Research), Thomas A. Cebula(United States Food and Drug Administration), Walter Koch(United States Food and Drug Administration), A. W. Andrews(LabCorp (United States)), Jane S. Allen(Research Triangle Park Foundation), Larry K. Keefer(Frederick National Laboratory for Cancer Research)
Science
November 15, 1991
10.1126/science.1948068
Cited by 1,237

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.

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