DNAase I Hypersensitive Sites of the c-Ha-ras-1 Proto-Oncogene as Targets for Rapid Benzo[a]pyrene Binding and Repair

  • Michael I. Lerman
  • Richard L. Norman
  • Linda Stevens
  • Sherman F. Stinson
  • Umberto Saffiotti


A vast amount of data has been gathered on the binding of chemical carcinogens to DNA, on the formation of carcinogen-DNA adducts and on the repair mechanisms that remove the DNA lesions and restore the continuity and integrity of the DNA. The mechanisms responsible for the formation of reactive metabolites of carcinogens capable of interacting with target macromolecules have been identified and extensively studied for many types of carcinogens. Correlations have been demonstrated between the covalent binding of many chemicals to DNA and their mutagenic and carcinogenic activity, in vivo and in isolated cells and tissues of both animal and human origin. These correlations, however, are not sufficient to explain the variety of selective carcinogenic responses induced by many different carcinogens in different tissues and cell types. Furthermore, carcinogens bind to a vast number of cells in a target tissue, whereas the origin of a neoplastic cell population, growing into a tumor, is often traceable to a single cell. The role of many cofactors that modulate the carcinogenic response has been progressively better understood and multifactorial models for the process of carcinogenesis are now becoming more generally accepted. The interplay of the effects of different carcinogens, cofactors and host factors has been recognized in human and experimental carcinogenesis studies. For most of the known chemical carcinogens, the critical mechanism of action is thought to be the induction of specific DNA lesions. These may occur through carcinogen binding to nucleotides, through faulty DNA replication on a damaged template, and possibly through errors of repair.


Hypersensitive Site Hamster Liver Neoplastic Cell Population Hypersensitive Region Kirsten Murine Sarcoma Virus 
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Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Michael I. Lerman
    • 3
  • Richard L. Norman
    • 1
  • Linda Stevens
    • 2
  • Sherman F. Stinson
    • 2
  • Umberto Saffiotti
    • 2
  1. 1.Laboratory of Immunobiology, Div. of Cancer Biology and DiagnosisNational Cancer InstituteFrederickUSA
  2. 2.Industrial Hygiene LaboratoryMare Island Naval ShipyardVallejoUSA
  3. 3.Laboratory of Experimental Pathology, Division of Cancer EtiologyNational Cancer InstituteBethesdaUSA

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