Chronic hypoxia modulates tumour cell radioresponse through cytokine-inducible nitric oxide synthase

Br J Cancer. 2001 Apr 20;84(8):1122-5. doi: 10.1054/bjoc.2000.1719.

Abstract

Chronic hypoxia up-regulated the mRNA and protein expression of inducible nitric oxide synthase (iNOS) in EMT-6 tumour cells exposed to interferon (IFN)-gamma and interleukin (IL)-I beta. Low concentrations of cytokines (1 unit ml(-1)) in 1% but not in 21% oxygen induced a remarkable increase in NO production and a 1.8-fold hypoxic cell radiosensitization. Therefore, chronic hypoxia may potentially be exploited to increase tumour cell radioresponse through the cytokine-inducible iNOS pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Blotting, Western
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Cytokines / pharmacology*
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Gene Expression Regulation, Enzymologic / drug effects
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • Nitric Oxide Synthase / drug effects*
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Nitrites / metabolism
  • Oxygen / pharmacology*
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / radiation effects

Substances

  • Cytokines
  • Interleukin-1
  • Nitrites
  • RNA, Messenger
  • Interferon-gamma
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Oxygen