Chronic hypoxia modulates tumour cell radioresponse through cytokine-inducible nitric oxide synthase.
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.
Berge
D L
DL
Cancer Research Unit, Academic Hospital Free University Brussels, Oncology Center, Laarbeeklaan 101, Brussels, 1090, Belgium.
De Ridder
M
M
Verovski
V N
VN
Janssens
M Y
MY
Monsaert
C
C
Storme
G A
GA
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects
D016207:Cytokines; D007375:Interleukin-1; D009573:Nitrites; D012333:RNA, Messenger; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D010100:Oxygen