Nitric oxide synergistically enhances DNA strand breakage induced by polyhydroxyaromatic compounds, but inhibits that induced by the Fenton reaction

Archives of Biochemistry and Biophysics
Y Yoshie, H Ohshima

Abstract

Reactive oxygen and nitrogen species play an important role in many human diseases including cancer. We have found that incubation of pBR322 plasmid DNA with a nitric oxide (NO)-releasing compound such as diethylamine NONOate and a polyhydroxyaromatic compound such as catechol, 1,4-hydroquinone, or pyrogallol caused synergistic induction of single-strand breakage, whereas either compound alone induced much less breakage. Phenol, resorcinol, or guaiacol (O-methylcatechol) did not exhibit this synergistic effect of DNA damage with NO. The strand breakage induced by NO with pyrogallol was prevented by excess superoxide dismutase, carboxy-PTIO (an NO-trapping agent), or anti-oxidants (urate, ascorbate). Possible mechanisms for the induction of this synergistic effect of NO and polyhydroxyaromatic compounds on the strand breakage are proposed, including involvement of peroxynitrite formed from NO and O2.- derived from autooxidation of polyhydroxyaromatics. This pathway for generation of reactive species from NO and catechol-type compounds (e.g., L-dopa, catechol-estrogen) may be important in many pathological conditions, because both compounds are concurrently formed or present in vivo. On the other hand, NO dose-dependently inhibit...Continue Reading

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Mar 1, 2005·Environmental Health and Preventive Medicine·Shinji Oikawa
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