Inducible nitric oxide synthase (iNOS) mediates the early increase of blood supply (EIBS) in colon carcinogenesis

FEBS Lett. 2007 Aug 7;581(20):3857-62. doi: 10.1016/j.febslet.2007.07.012. Epub 2007 Jul 16.


We have recently demonstrated that dramatic alteration in mucosal microvascular blood content termed early increase in blood supply (EIBS) is a hallmark of early colon carcinogenesis. In the current study, we elucidate the mechanism of EIBS by assessing iNOS/nitric oxide axis in the histologically normal colonic mucosa of rats treated with the colon-specific carcinogen, azoxymethane. We demonstrate that there was a strong temporal correlation between EIBS and iNOS expression/activity. Importantly, we also observed that short-term treatment with nitric oxide inhibitor abrogated EIBS. These data indicate that iNOS induction may have a critical role in augmenting the predysplastic mucosal blood supply and thereby fostering colon carcinogenesis.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Azoxymethane / toxicity
  • Carcinogens / toxicity
  • Colonic Neoplasms / blood supply*
  • Colonic Neoplasms / etiology*
  • Colonic Neoplasms / pathology
  • Enzyme Inhibitors / pharmacology
  • Immunohistochemistry
  • Light
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / metabolism*
  • Rats
  • Rats, Inbred F344
  • Scattering, Radiation
  • Time Factors


  • Carcinogens
  • Enzyme Inhibitors
  • Nitric Oxide Synthase Type II
  • Azoxymethane
  • NG-Nitroarginine Methyl Ester