Carcinogenesis, Vol 18, 1359-1363, Copyright © 1997 by Oxford University Press
Y Yoshie and H Ohshima
Cigarette smoking is a major cause of human cancer at a variety of sites,
although its carcinogenic mechanisms remains unestablished. Cigarette smoke
can be divided into two phases, gas phase and particulate matter (tar).
Both phases contain high concentrations of oxidants and free radicals,
especially nitric oxide (NO) and nitrogen oxides in the gas phase and
quinone/hydroquinone complex in the tar. We have found that incubation of
pBR322 plasmid DNA with aqueous extracts of cigarette tar and a
NO-releasing compound (diethylamine NONOate) caused synergistic induction
of DNA single-strand breakage, whereas either cigarette tar alone or NO
alone induced much less strand breakage. This synergistic effect of
cigarette tar and NO on DNA strand breakage was prevented by high
concentrations of superoxide dismutase, carboxy-PTIO (an NO-trapping agent)
or N-acetylcysteine, whereas hydroxyl radical scavengers such as
dimethylsulfoxide, ethanol and D- mannitol did not show inhibitory effects.
Possible mechanisms for this synergistic effect mediated by cigarette tar
and NO are proposed, including involvement of peroxynitrite, which is a
strong oxidant and nitrating agent formed rapidly by the reaction between
NO and O2.-. NO is present in the gas phase of smoke and may be formed by a
constitutive or inducible NO synthase in the lung, whereas O2.- is
generated by auto-oxidation of polyhydroxyaromatic compounds such as
catechol and 1,4-hydroquinone present in cigarette tar. Thus, potent
reactive species including peroxynitrite formed by the interaction between
cigarette tar and NO may play an important role in smoking- related
diseases including lung cancer.
ARTICLES
Synergistic induction of DNA strand breakage by cigarette tar and nitric oxide
Unit of Endogenous Cancer Risk Factors, International Agency for Research on Cancer, Lyon, France.
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