Prevention of Peroxide Produced DNA Strand Scission in Human Tumor Cells by Lipoxygenase Inhibitors

  • M. A. Baker
Part of the Developments in Oncology book series (DION, volume 67)


Hydrogen peroxide, radiation, and many cancer chemotherapy drugs cause oxidative damage to cells including DNA strand breaks. Hydrogen peroxide is several orders of magnitude more toxic to cells at 37° C than at 0° C (1). At low doses, these agents produce mutation and transformation in various cells. The phorbol esters, transforming agents which are structurally unrelated to peroxide have also been reported to produce oxidative damage in cells. Many of the actions of tumor necrosis factor, a peptide with diverse cellular effects, appear to be mediated through “free radical-like” damage. Other cellular events, including protein kinase C translocation, the induction of proto-oncogene fos, and intracellular Ca2+ increase result from treatment with peroxides, transforming agents and various growth factors (2). It seems likely then that the DNA strand breaks produced by radiation, xenobiotics, or peroxides cannot be exclusively attributed to chemical interactions. That is, the “indirect” action of radiation may be mediated through rapidly initiated cellular mechanisms which lead to DNA scission rather than by hydroxyl radical reactions on the DNA molecule itself. The following experiments support these hypotheses.


Strand Break Single Strand Break Lipoxygenase Product Phosphate Buffer Salt Solution Strand Break Induction 
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Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • M. A. Baker
    • 1
  1. 1.Department of Radiation OncologyUniversity of PennsylvaniaPhiladelphiaUSA

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