Mapping the role of NAD metabolism in prevention and treatment of carcinogenesis

  • Elaine L. Jacobson
  • W. Melissa Shieh
  • Arnold C. Huang
Part of the Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease book series (DMCB, volume 30)

Abstract

Studies presented here show that cellular NAD, which we hypothesize to be the relevant biomarker of niacin status, is significantly lower in humans than in the commonly studied animal models of carcinogenesis. We show that nicotinamide and the resulting cellular NAD concentration modulate expression of the tumor suppressor protein, p53, in human breast, skin, and lung cells. Studies to determine the optimal NAD concentrations for responding to DNA damage in breast epithelial cells reveal that DNA damage appears to stimulate NAD biosynthesis and that recovery from DNA damage occurs several hours earlier in the presence of higher NAD or in cells undergoing active NAD biosynthesis. Finally, analyses of normal human skin tissue from individuals diagnosed with actinic kératoses or squamous cell carcinomas show that NAD content of the skin is inversely correlated with the malignant phenotype. Since NAD is important in modulating ADP-ribose polymer metabolism, cyclic ADP-ribose synthesis, and stress response proteins, such as p53, following DNA damage, understanding how NAD metabolism is regulated in the human has important implications in developing both prevention and treatment strategies in carcinogenesis.

Key words

skin lung and breast cancer p53 expression cyclic ADP-ribose poly(ADP-ribose) metabolism niacin status 

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Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Elaine L. Jacobson
    • 1
    • 2
    • 3
    • 4
    • 5
  • W. Melissa Shieh
    • 1
  • Arnold C. Huang
    • 2
  1. 1.Department of Clinical SciencesLexingtonUSA
  2. 2.Multidisciplinary Program in Nutritional SciencesLexingtonUSA
  3. 3.Advanced Science and Technology Commercialization CenterLexingtonUSA
  4. 4.Lucille P. Markey Cancer CenterUniversity of KentuckyLexingtonUSA
  5. 5.University of KentuckyLexingtonUSA

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