DNA Deaminating Ability and Genotoxicity of Nitric Oxide and its Progenitors

TLDR

Nitric oxide is a bioregulatory agent and environmental pollutant that can induce genomic alterations. In vitro, NO deaminated nucleosides, nucleotides, and DNA at physiological pH, and in vivo exposure of Salmonella TA1535 to NO‑releasing compounds confirmed similar DNA damage. NO exposure caused >99% C→T transitions in Salmonella, proving mutagenic and indicating that widespread NO exposure may contribute to deamination‑related disease and cancer.

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.