Document Detail


Detection of in vivo genotoxicity of endogenously formed N-nitroso compounds and suppression by ascorbic acid, teas and fruit juices.
MedLine Citation:
PMID:  12948815     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The genotoxicity of endogenously formed N-nitrosamines from secondary amines and sodium nitrite (NaNO(2)) was evaluated in multiple organs of mice, using comet assay. Groups of four male mice were orally given dimethylamine, proline, and morpholine simultaneously with NaNO(2). The stomach, colon, liver, kidney, urinary bladder, lung, brain, and bone marrow were sampled 3 and 24 h after these compounds had been ingested. Although secondary amines and the NaNO(2) tested did not yield DNA damage in any of the organs tested, DNA damage was observed mainly in the liver following simultaneous oral ingestion of these compounds. The administration within a 60 min interval also yielded hepatic DNA damage. It is considered that DNA damage induced in mouse organs with the coexistence of amines and nitrite in the acidic stomach is due to endogenously formed nitrosamines. Ascorbic acid reduced the liver DNA damage induced by morpholine and NaNO(2). Reductions in hepatic genotoxicity of endogenously formed N-nitrosomorpholine by tea polyphenols, such as catechins and theaflavins, and fresh apple, grape, and orange juices were more effective than was by ascorbic acid. In contrast with the antimutagenicity of ascorbic acid in the liver, ascorbic acid yielded stomach DNA damage in the presence of NaNO(2) (in the presence and absence of morpholine). Even if ascorbic acid acts as an antimutagen in the liver, nitric oxide (NO) formed from the reduction of NaNO(2) by ascorbic acid damaged stomach DNA.
Authors:
Koh-ichi Ohsawa; Shin-ya Nakagawa; Masaaki Kimura; Chihiro Shimada; Shuji Tsuda; Kazumi Kabasawa; Satomi Kawaguchi; Yu F Sasaki
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Mutation research     Volume:  539     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  2003 Aug 
Date Detail:
Created Date:  2003-09-01     Completed Date:  2003-10-08     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  65-76     Citation Subset:  IM    
Affiliation:
Toxicology Laboratory, Taisho Pharmaceutical Co Ltd, Yoshino-cho 1-403, Kita-ku, Saitama-shi, Saitama 331-9530, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Ascorbic Acid / pharmacology*
Beverages*
Comet Assay
DNA Damage*
Fruit*
Liver / drug effects
Male
Mice
Morpholines / pharmacokinetics,  toxicity
Muscarinic Antagonists / pharmacology
Mutagenicity Tests
Mutagens
Nitrosamines / metabolism,  toxicity*
Proline / pharmacokinetics,  toxicity
Sodium Nitrite / pharmacokinetics,  toxicity
Tea*
Chemical
Reg. No./Substance:
0/Morpholines; 0/Muscarinic Antagonists; 0/Mutagens; 0/Nitrosamines; 0/Tea; 110-91-8/morpholine; 13256-06-9/N,N-diamylnitrosamine; 147-85-3/Proline; 50-81-7/Ascorbic Acid; 7632-00-0/Sodium Nitrite

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


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