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In-vitro assays to detect alkylating and mutagenic activities of dietary components nitrosated in situ

Please always quote using this URN: urn:nbn:de:bvb:20-opus-86194
  • Nitrosation of dietary components has been combined with the 4-(para-nitrobenzyl)pyridine (NBP) colorimetric test for screening alkylating agents and with the Ames test for the detection of mutagenic activity. This allowed the investigation of short-hved nitrosation products of dietary components which generate electrophilic degradation products requiring no metabolic activation (natural amino acids and some derivatives, ureas, guanidines, primary alkyl and aryl amines). In a first system, precursor, nitrous acid and NBP were presentNitrosation of dietary components has been combined with the 4-(para-nitrobenzyl)pyridine (NBP) colorimetric test for screening alkylating agents and with the Ames test for the detection of mutagenic activity. This allowed the investigation of short-hved nitrosation products of dietary components which generate electrophilic degradation products requiring no metabolic activation (natural amino acids and some derivatives, ureas, guanidines, primary alkyl and aryl amines). In a first system, precursor, nitrous acid and NBP were present simultaneously. All amino acids tested, except glutamic acid and glutamine, gave positive results. The reactivities spanned more than three orders of magnitude, with the aromatic amino acids and methionine the most active; two primary amines, tryptamine and histamine, were also strongly reactive. All guanidines tested, except the amino acid arginine, gave negative results. A second system consisted of two phases: NBP was added only after destruction of residual nitrite and adjustment of the pH to neutrality. This system was useful for the study of ureas, which are stable in acid but not in neutral media. The range of responses covered more than two orders of magnitude. Most amino acids and primary amines also gave positive results, but could be assessed only after analysing the kinetics of the competing reactions and choosing appropriate reaction times. In a third system, Salmonella typhimurium strain TA1OO replaced NBP. Representatives of the class of amino acids, ureas, the primary amine tryptamine, and aniline became higbly mutagenic upon nitrosation. Methylguanidine was only weakly mutagenic under the present assay conditions. The results indicate that further studies with unstable nitrosation products of dietary components are required to understand more thoroughly the role of endogenous nitrosation in gastric cancer.show moreshow less

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Metadaten
Author: S. E. Shephard, M. E. Hegi, Werner K. Lutz
URN:urn:nbn:de:bvb:20-opus-86194
Document Type:Book article / Book chapter
Faculties:Medizinische Fakultät / Institut für Pharmakologie und Toxikologie
Language:English
Year of Completion:1987
Source:In: Relevance of N-nitroso compounds to human cancer / ed. H. Bartsch. - Lyon: IARC, 1987. - S. 232-236. - (Centre International de Recherche sur le Cancer <Lyon>: IARC scientific publications ; 84). - ISBN 92-832-1184-7
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
GND Keyword:Medizin
Release Date:2014/06/12
Licence (German):License LogoDeutsches Urheberrecht