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Detection of carcinogen–DNA adducts by radioimmunoassay

Nature volume 270, pages 186–188 (1977)Cite this article

Abstract

COVALENT binding of carcinogen to nucleic acids is believed to be an essential component of the carcinogenic process1, so it is desirable to have highly sensitive and specific methods for detecting such adducts in cells and tissues exposed to known and suspected carcinogens. We describe here a radioimmunoassay (RIA) capable of detecting nanogram amounts of DNA adducts resulting from the covalent binding of the carcinogen N-2-acetylaminofluorene (AAF). AAF and its activated derivative N-acetoxy-AAF (N-Ac-AAF) are potent carcinogens2 and mutagens3,4, and transform cells in culture5,6. DNA obtained from rat liver following in vivo exposure to AAF, and DNA exposed in vitro to N-Ac-AAF contain as the major (80%) adduct N-(deoxyguanosin-8-yl)-acetylaminofluorene (dG-8-AAF)7–9 and a minor (20%) adduct 3-(deoxyguanosin-N2−yl)-acetylaminofluorene (dG-N2-AAF)10. These two types of modification produce markedly different conformational effects on the DNA helix2,11,12. The major adduct, recognised by single strand-specific nucleases in vitro13,14 and DNA repair enzymes in vivo9,15 was used as the immunogen in this study.

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Authors and Affiliations

  1. In Vitro Pathogenesis Section, Experimental Pathology Branch, Division of Cancer Cause and Prevention, National Cancer Institute, Bethesda, Maryland, 20014

    MIRIAM C. POIRIER & STUART H. YUSPA

  2. Columbia University College of Physicians and Surgeons, Health Sciences Centre, 701 West 168th Street, New York, New York, 10032

    I. BERNARD WEINSTEIN

  3. Rockefeller University, 1230 York Avenue, New York, New York, 10011

    STEVEN BLOBSTEIN

Authors
  1. MIRIAM C. POIRIER
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  2. STUART H. YUSPA
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  3. I. BERNARD WEINSTEIN
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  4. STEVEN BLOBSTEIN
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POIRIER, M., YUSPA, S., WEINSTEIN, I. et al. Detection of carcinogen–DNA adducts by radioimmunoassay. Nature 270, 186–188 (1977). https://doi.org/10.1038/270186a0

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