Involvement of Reactive Oxygen Intermediates in the Mutagenicity of Tumor Promoters

  • Neal Wallis Biggart
  • Edwin C. MurphyJr.
Part of the Basic Life Sciences book series (BLSC, volume 49)


Reactive oxygen intermediates have been strongly implicated in tumor promotion not only because many tumor promoters generate free radicals either directly or indirectly, but also because many antipromoters are anti-oxidants which inhibit the reactivity of oxygen radicals (for reviews, see references 1–4). Tumor promoting agents can be distinguished from initiating agents on the basis of the DNA damage they induce; whereas true initiators cause irreversible, heritable changes through mutation, tumor promoters are clastogenic, i.e., cause DNA strand breaks, and this damage is reversible to some degree. The clastogenic action of promoters is thought to be due at least in part to the generation of reactive oxygen intermediates and perhaps to the secondary generation of other reactive intermediates from interaction with cellular macromolecules such as membrane lipids. Type II promoters, such as benzoyl peroxide, generate oxygen radicals directly in the target cell without the mediation of other effectors. Type I promoters, such as the phorbol esters, act indirectly via effectors such as protein kinase c to generate superoxide, perhaps as a by-product of the arachidonic cascade. In addition, type I promoters stimulate the respiratory burst of phagocytic cells, and the reactive oxygen (superoxide, hydrogen peroxide) produced during this burst can then act on nearby cells.


Benzoyl Peroxide Cadmium Chloride Reactive Oxygen Intermediate Splice Efficiency Sodium Chromate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    H.C. Bimboim, Importance of DNA strand break damage in tumor promotion, in: “Radioprotectors and Anticarcinogens”, O.F. Nygaard and M.G. Simic, eds. Academic Press, New York (1983).Google Scholar
  2. 2.
    E.S. Copeland, ed., NIH Workshop Report, Free radicals in promotion—a chemical pathology study section workshop, Cancer Res. 43:5631 (1983).Google Scholar
  3. 3.
    T.J. Slaga, ed., “Mechanisms of Tumor Promotion”, Vols I–IV, CRC Press, Boca Raton (1984).Google Scholar
  4. 4.
    P.A. Cerutti, Prooxidant states and tumor promotion, Science 227:375Google Scholar
  5. 5.
    F.W. Sunderman Jr., Carcinogenic effects of metals, Fed. Proc. 37:40Google Scholar
  6. 6.
    N.W. Biggart, G.E. Gallick, and E.C. Murphy Jr., Nickel-induced heritable alterations in retroviral transforming gene expression. J. Virology 61:2378 (1981).Google Scholar
  7. 7.
    N.W. Biggart and E.C. Murphy, Jr., Analysis of metal-induced alterations in either structure or expression of a stably integrated provirus in a mammalian cell line, Mutation Res., in press (1988).Google Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Neal Wallis Biggart
    • 1
  • Edwin C. MurphyJr.
    • 2
  1. 1.Department of BiologySan Diego State UniversitySan DiegoUSA
  2. 2.M.D. Anderson Hospital and Tumor InstituteUniversity of Texas Cancer SystemHoustonUSA

Personalised recommendations