Reactive oxygen species in choline deficiency induced carcinogenesis and nitrone inhibition

  • Robert A. Floyd
  • Yashige Kotake
  • Kenneth Hensley
  • Dai Nakae
  • Yoichi Konishi
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 37)


Reactive oxygen species and free radical processes have been considered important in cancer development for many years. Much research demonstrates that the choline-deficiency induced hepatocarcinogenesis model prominently involves reactive oxygen species. We present a summary of results obtained in our original studies of this model over the last 4 years. We have shown that a-phenyl-tert-butyl nitrone (PBN) and some of its hydroxylated derivatives (the 4- and 3-hydroxylated compounds) prevent hepatocarcinogenesis in this model. Mechanistic studies have demonstrated that isolated mitochondria from the livers of rats fed the choline-deficiency defined amino acid diet produce significantly much more H202per NADH reducing equivalents oxidized. Based on these observations, we postulate that H202is a primary carcinogenic factor in this model. Based on studies of the action of PBN on isolated mitochondria, we postulate that the inhibiting action of PBN involves suppression of H202 production of mitochondria and generally decreasing the oxidative stress within the preneoplastic lesions. The net effect of the activity of the nitrone compounds appears to be due to their ability to shift the apoptosis/neoplastic tendency balance toward apoptosis of the cells within the preneoplastic lesions. This is considered to be the primary reason the size of the preneoplastic lesions are significantly decreased and why the nitrones are potent anti-carcinogenic agents in this model. (Mol Cell Biochem 234/235: 195–203, 2002)

Key words

choline deficiency hepatocarcinogenesis preneoplastic lesions reactive oxygen species liver cancer hydrogen peroxide a-phenyl-tert-butyl nitrone 


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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Robert A. Floyd
    • 1
    • 2
  • Yashige Kotake
    • 1
  • Kenneth Hensley
    • 1
  • Dai Nakae
    • 3
  • Yoichi Konishi
    • 3
  1. 1.Free Radical Biology and Aging Research ProgramOklahoma Medical Research FoundationUSA
  2. 2.Department of Biochemistry and Molecular BiologyUniversity of Oklahoma Health Sciences CenterUSA
  3. 3.Nara Medical UniversityNaraJapan

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