The effect of potassium diazoacetate on human peripheral lymphocytes, human adenocarcinoma colon caco-2 cells, and rat primary colon cells in the comet assay

In previous studies, N‐(N′‐acetyl‐L‐propyl)‐N‐nitrosoglycine (APNG) has been shown to be a potent mutagen in a variety of genotoxicity assays and a carcinogen in a limited cancer study. APNG decomposes to a carboxymethyldiazonium ion, which can also be generated from potassium diazoacetate (KDA). KD...

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Published in:Teratogenesis, carcinogenesis, and mutagenesis carcinogenesis, and mutagenesis, 1999, Vol.19 (2), p.137-146
Main Authors: Anderson, Diana, Hambly, Richard J., Yu, Tian-Wei, Thomasoni, Federica, Shuker, David E.G.
Format: Article
Language:English
Subjects:
Adult
Animals
APNG
Azo Compounds - pharmacology
Biological and medical sciences
Caco-2 Cells
Cells, Cultured
Chemical mutagenesis
Colon - drug effects
Comet assay
DNA Damage
Dose-Response Relationship, Drug
Electrophoresis
Female
genotoxicity assays
Glycine - analogs & derivatives
Glycine - pharmacology
Humans
KDA
Lymphocytes - drug effects
Lymphocytes - ultrastructure
Medical sciences
mutagen
Mutagenicity Tests
Rats
Toxicology
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Summary:In previous studies, N‐(N′‐acetyl‐L‐propyl)‐N‐nitrosoglycine (APNG) has been shown to be a potent mutagen in a variety of genotoxicity assays and a carcinogen in a limited cancer study. APNG decomposes to a carboxymethyldiazonium ion, which can also be generated from potassium diazoacetate (KDA). KDA is particularly interesting because it is a stable nitrosated derivative of glycine, one of the most common dietary amino acids. KDA has been shown to produce more O6 carboxymethyl‐ and O6 methyl‐adducts than APNG, so it was anticipated that it might also be a potent genotoxic agent. Thus in the present study KDA has been investigated in the single cell gel electrophoresis (Comet) assay, which primarily measures DNA strand breakage. Since KDA has been shown to be formed in the gut, the genotoxic effects of KDA were investigated in vitro in human adenocarcinoma colon Caco‐2 cells, and in rat primary colon cells and compared to responses from human peripheral lymphocytes. KDA induced DNA damage in the three cell types, confirming that KDA is genotoxic in a range of mammalian cells. Teratogenesis Carcinog. Mutagen. 19:137–146, 1999. © 1999 Wiley‐Liss, Inc.
ISSN:0270-3211
1520-6866
DOI:10.1002/(SICI)1520-6866(1999)19:2<137::AID-TCM6>3.0.CO;2-2