Document Detail


In-vivo nitrosation of amines in mice by inhaled nitrogen dioxide and inhibition of biosynthesis of N-nitrosamines.
MedLine Citation:
PMID:  6533019     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Inhalation of nitrogen dioxide (NO2) by mice administered orally morpholine (MOR) or dimethylamine (DMA) resulted in the biosynthesis of N-nitrosomorpholine (NMOR) or N-nitrosodimethylamine (NDMA), respectively, as determined by the analysis of frozen whole-mouse powder, using gas chromatography with a Thermal Energy Analyzer detector. Significant levels of NMOR were detected following exposure of mice to 0.38 mg/m3 NO2 for 0.5 h (26 ng NMOR/mouse) and there was a two-fold increase when NO2 exposure was extended to 4 h. NMOR levels also increased in a time-dependent manner at 28.4 and 47.3 mg/m3 NO2 exposure levels, reaching a maximum of 450 and 725 ng NMOR/mouse, respectively, at 4 h. Oral administration of sodium ascorbate (50-250 mg), ammonium sulfamate (50-100 mg) or DL-alpha-tocopherol (67-167 mg) immediately after MOR or DMA, but prior to NO2 exposure, significantly inhibited both NMOR and NDMA biosynthesis, sulfamate being the most effective (greater than 90% NMOR and NDMA inhibition), followed by ascorbate (83-90% NMOR and 58-90% NDMA inhibition) and alpha-tocopherol (22-42% NMOR and 46-69% NDMA inhibition). Low levels of NDMA were found in untreated control mice (less than 13 ng/mouse) and in most samples of commercially obtained animal feed (10-15 micrograms/kg); NMOR, however, was not detectable or was detected in negligible amounts in these cases. Various control experiments indicated that most of the recovered nitrosamine resulted from in-vivo nitrosation in mice, with only up to 1-2% of NMOR and approximately 10% of NDMA yields being attributed to artefact formation, possibly during work-up of the mouse-powder samples.
Authors:
Z M Iqbal
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  IARC scientific publications     Volume:  -     ISSN:  0300-5038     ISO Abbreviation:  IARC Sci. Publ.     Publication Date:  1984  
Date Detail:
Created Date:  1985-06-20     Completed Date:  1985-06-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8009542     Medline TA:  IARC Sci Publ     Country:  FRANCE    
Other Details:
Languages:  eng     Pagination:  291-300     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Chromatography, Gas
Dimethylamines / metabolism,  pharmacology
Dimethylnitrosamine / metabolism
Mice
Morpholines / metabolism,  pharmacology
Nitrogen Dioxide / metabolism*
Nitrosamines / metabolism*
Chemical
Reg. No./Substance:
0/Dimethylamines; 0/Morpholines; 0/Nitrosamines; 10102-44-0/Nitrogen Dioxide; 59-89-2/N-nitrosomorpholine; 62-75-9/Dimethylnitrosamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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