PMID- 9459179 OWN - NLM STAT- MEDLINE DCOM- 19980227 LR - 20190720 IS - 0304-3835 (Print) IS - 0304-3835 (Linking) VI - 121 IP - 1 DP - 1997 Dec 16 TI - Transient block of respiratory chain by cyanide triggers NADPH-diaphorase activity (a marker for nitric oxide synthase) in Dunning rat prostatic epithelium. PG - 91-7 AB - Synthesis of nitric oxide (NO) has been shown in the glandular epithelium of human prostate, with highest levels in the peripheral zone. This location is believed to be the main source of prostatic cancer. The ability of stromal cells to produce NO may contribute to the malignant process. Since solid tumours are prone to hypoxia and malignant progression, experiments were undertaken to test the effect of respiratory block on the induction of nitric oxide synthase (NOS) by a Dunning rat prostatic epithelial line. A metastatic phenotype (Mat-LyLu) was treated in vitro with brief exposure to cyanide in order to mimic transient hypoxic stress. NADPH-diaphorase activities in paraformaldehyde-fixed cells was used to follow the expression of NOS. NADPH-diaphorase activity was found to be inducible by a range of factors, including mechanical damage and infection of cultures. Cyanide induced a dose-dependent staining that was statistically greater than in untreated cells. Consistent with diaphorase staining being a marker for the inducible isoform of NOS (iNOS), induction and enhancement of staining, respectively, was observed in response to treatment with lipopolysaccharide or withdrawal of dexamethasone supplement. Results demonstrate that prostatic epithelia can be triggered in culture to express iNOS by transient oxidative stress in the form of respiratory poisoning by NaCN. Paradoxically, nitric oxide production by epithelia within hypoxic zones of solid tumours may contribute to the promotion and/or inhibition of tumorigenesis. FAU - Downing, J E AU - Downing JE AD - Department of Biology, Imperial College, London, UK. j.downing@ic.ac.uk LA - eng GR - Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Cancer Lett JT - Cancer letters JID - 7600053 RN - 0 (Cyanides) RN - 0 (Lipopolysaccharides) RN - 7S5I7G3JQL (Dexamethasone) RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nos2 protein, rat) RN - EC 1.6.99.1 (NADPH Dehydrogenase) SB - IM MH - Animals MH - Cell Hypoxia/*physiology MH - Cyanides/pharmacology MH - Dexamethasone/pharmacology MH - Dose-Response Relationship, Drug MH - Electron Transport/drug effects/*physiology MH - Histocytochemistry MH - Lipopolysaccharides/pharmacology MH - Male MH - NADPH Dehydrogenase/*metabolism MH - Nitric Oxide Synthase/*metabolism MH - Nitric Oxide Synthase Type II MH - Prostatic Neoplasms/enzymology/*pathology MH - Rats MH - Rats, Inbred Strains MH - Time Factors MH - Tumor Cells, Cultured EDAT- 1998/02/12 00:00 MHDA- 1998/02/12 00:01 CRDT- 1998/02/12 00:00 PHST- 1998/02/12 00:00 [pubmed] PHST- 1998/02/12 00:01 [medline] PHST- 1998/02/12 00:00 [entrez] AID - S0304-3835(97)00339-X [pii] AID - 10.1016/s0304-3835(97)00339-x [doi] PST - ppublish SO - Cancer Lett. 1997 Dec 16;121(1):91-7. doi: 10.1016/s0304-3835(97)00339-x.