Vitamin D receptor activity and prevention of colonic hyperproliferation and oxidative stress

Food Chem Toxicol. 2002 Aug;40(8):1191-6. doi: 10.1016/s0278-6915(02)00030-3.


Unimpaired vitamin D action has been implicated in human cancer prevention. We have previously demonstrated the effectiveness of 1 alpha-dihydroxyvitamin D3 (1,25-D3) to reduce proliferation and increase differentiation in human colon cancer cells. The aim of this study was to investigate, on the one hand, expression of the vitamin D receptor (VDR) and of 25-hydroxyvitamin D(3)-1 alpha-hydroxylase (1 alpha-hydroxylase) in human normal and malignant colonic tissue and, on the other hand, to determine consequences of reduced or lacking VDR action in a VDR knockout mouse model. In low-grade malignancies of the human colon we found increased VDR and 1 alpha-hydroxylase mRNA expression. However, in late-stage high-grade tumors the vitamin D system is severely compromised. In the mouse colon we found an inverse relationship between VDR levels and proliferation in colon descendens, a tissue known to be specifically affected by nutrients during carcinogenesis. Expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, was significantly augmented with complete loss of VDR. These data suggest that genomic 1,25-D(3) action is necessary to protect against nutrition-linked hyperproliferation and oxidative DNA damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism*
  • 8-Hydroxy-2'-Deoxyguanosine
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adenocarcinoma / prevention & control
  • Animals
  • Cell Differentiation
  • Cell Division / drug effects
  • Colon / cytology
  • Colon / metabolism
  • Colon / pathology*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Colorectal Neoplasms / prevention & control
  • DNA Damage / drug effects
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / metabolism
  • Disease Models, Animal
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Knockout
  • Oxidative Stress / drug effects*
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction


  • Receptors, Calcitriol
  • 8-Hydroxy-2'-Deoxyguanosine
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Deoxyguanosine