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Science 15 November 1991:
Vol. 254. no. 5034, pp. 1001 - 1003
DOI: 10.1126/science.1948068
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Articles

Science, Vol 254, Issue 5034, 1001-1003
Copyright © 1991 by American Association for the Advancement of Science

articles

DNA deaminating ability and genotoxicity of nitric oxide and its progenitors

DA Wink, KS Kasprzak, CM Maragos, RK Elespuru, M Misra, TM Dunams, TA Cebula, WH Koch, AW Andrews, JS Allen, and al. et

Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, MD 21702.

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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J Natl Cancer Inst 91, 86-88
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Participation of Nitric Oxide in the Mucosal Injury of Rat Intestine Induced by Ischemia-Reperfusion.
K. Takada, K. Yamashita, Y. Sakurai-Yamashita, K. Shigematsu, Y. Hamada, K. Hioki, and K. Taniyama (1998)
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PNAS 95, 7368-7373
   Abstract »    Full Text »    PDF »
Nitric Oxide-induced Deamination of Cytosine and Guanine in Deoxynucleosides and Oligonucleotides.
J. L. Caulfield, J. S. Wishnok, and S. R. Tannenbaum (1998)
J. Biol. Chem. 273, 12689-12695
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Accelerated reaction of nitric oxide with O2 within the hydrophobic interior of biological membranes.
X. Liu, M. J. S. Miller, M. S. Joshi, D. D. Thomas, and J. R. Lancaster Jr. (1998)
PNAS 95, 2175-2179
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Hepatitis B virus X protein and p53 tumor suppressor interactions in the modulation of apoptosis.
L. W. Elmore, A. R. Hancock, S.-F. Chang, X. W. Wang, S. Chang, C. P. Callahan, D. A. Geller, H. Will, and C. C. Harris (1997)
PNAS 94, 14707-14712
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