PMID- 8608550
OWN - NLM
STAT- MEDLINE
DCOM- 19960530
LR  - 20171116
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 77
IP  - 8 Suppl
DP  - 1996 Apr 15
TI  - Excessive production of nitric oxide in rat solid tumor and its implication in 
      rapid tumor growth.
PG  - 1598-604
AB  - BACKGROUND: Rapid tumor growth is caused by angiogenesis factors, growth factors, 
      etc. We previously reported a possible connection between nitric oxide (NO) and 
      enhanced vascular permeability in solid tumor. In the present experiment, the 
      role of NO in solid tumor pathology was further investigated in animal tumor. 
      METHODS: To identify NO formed in solid tumor (AH136B) implanted in the feet of 
      rats, electron paramagnetic resonance (EPR) spectroscopy was performed directly 
      on the frozen tumor tissue at 110K by measuring endogenous nitrosyl iron-sulfur 
      complexes, and by using exogenously added NO capturing agents, i.e., 
      diethyldithiocarbamate (DETC)-Fe2+ and N-(dithiocarboxy) sarcosine (DTCS)-Fe2+ 
      complexes. Induction of inducible isoform of nosymthase iNOS mRNA was examined 
      with reverse transcriptase-polymerase chain reaction (RT-PCR) combined with 
      Southern blot analysis. In addition, vascular permeability was assessed by 
      measuring extravasation of 51Cr-labeled bovine serum albumin in solid tumor. 
      RESULTS: Strong EPR signals from NO adducts of DETC-Fe2+ and DTCS-Fe2+ as well as 
      strong signals from NO-hemoglobin and dinitrosyl iron sulfur complex were 
      generated by tumor. The signal height of NO-(DTCS)2-Fe2+ observed in AH136B solid 
      tumor was increased as the tumor gained up to 1.75 g. Induction of iNOS mRNA 
      expression was confirmed by the above methods. Enhanced vascular permeability was 
      suppressed by NOS inhibitors N omega- monomethyl-L-arginine or 
      S-methylisothiourea sulfate and augmented with administration of L-arginine. 
      CONCLUSIONS: Excessive NO production by iNOS in solid tumor was identified 
      unequivocally by EPR spectroscopy. NO formed in solid tumor can be involved in 
      enhanced vascular permeability and increased blood flow, and hence sustain tumor 
      growth.
FAU - Doi, K
AU  - Doi K
AD  - Department of Surgery II, Kumamoto University, School of Medicine, Japan.
FAU - Akaike, T
AU  - Akaike T
FAU - Horie, H
AU  - Horie H
FAU - Noguchi, Y
AU  - Noguchi Y
FAU - Fujii, S
AU  - Fujii S
FAU - Beppu, T
AU  - Beppu T
FAU - Ogawa, M
AU  - Ogawa M
FAU - Maeda, H
AU  - Maeda H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Chromium Radioisotopes)
RN  - 0 (RNA, Messenger)
RN  - 27432CM55Q (Serum Albumin, Bovine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Blotting, Southern
MH  - Capillary Permeability
MH  - Cell Division/physiology
MH  - Chromium Radioisotopes
MH  - Molecular Sequence Data
MH  - Neoplasm Transplantation
MH  - Neoplasms, Experimental/*metabolism/*pathology
MH  - Nitric Oxide/*biosynthesis
MH  - Nitric Oxide Synthase/biosynthesis
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Serum Albumin, Bovine/pharmacokinetics
MH  - Transcription, Genetic
EDAT- 1996/04/15 00:00
MHDA- 2000/06/20 09:00
CRDT- 1996/04/15 00:00
PHST- 1996/04/15 00:00 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1996/04/15 00:00 [entrez]
AID - 10.1002/(SICI)1097-0142(19960415)77:8<1598::AID-CNCR27>3.0.CO;2-U [pii]
AID - 10.1002/(SICI)1097-0142(19960415)77:8<1598::AID-CNCR27>3.0.CO;2-U [doi]
PST - ppublish
SO  - Cancer. 1996 Apr 15;77(8 Suppl):1598-604. doi: 
      10.1002/(SICI)1097-0142(19960415)77:8<1598::AID-CNCR27>3.0.CO;2-U.