Differential response of flat and polypoid colitis-associated colorectal neoplasias to chemopreventive agents and heterocyclic amines

Cancer Lett. 2013 Jun 28;334(1):62-8. doi: 10.1016/j.canlet.2013.02.013. Epub 2013 Feb 13.

Abstract

Individuals with ulcerative colitis face an increased risk of developing colorectal cancer and would benefit from early chemopreventive intervention. Results from preclinical studies in the mouse model of dextran sulfate sodium-induced colitis demonstrate that flat and polypoid colitis-associated dysplasias arise via distinct genetic pathways, impacted by the allelic status of p53. Furthermore, flat and polypoid dysplasias vary in their response to induction by the heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and inhibition by 5-aminosalicylic acid, a common therapy for the maintenance of colitis patients. These data suggest that use of combination therapy is essential for the optimal inhibition of colitis-associated colorectal cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Amines / toxicity
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Apoptosis / drug effects
  • Carcinogens / toxicity
  • Cell Proliferation / drug effects
  • Colitis / chemically induced
  • Colitis, Ulcerative / complications*
  • Colitis, Ulcerative / drug therapy
  • Colitis, Ulcerative / pathology*
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / etiology*
  • Dextran Sulfate / toxicity
  • Disease Models, Animal
  • Humans
  • Meat Products
  • Mesalamine / pharmacology*
  • Mice
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Quinolines / toxicity

Substances

  • Amines
  • Anti-Inflammatory Agents, Non-Steroidal
  • Carcinogens
  • Quinolines
  • 2-amino-3-methylimidazo(4,5-f)quinoline
  • Mesalamine
  • Dextran Sulfate
  • Nitric Oxide Synthase Type II