Abstract
Photolysis of arylazides in aqueous media was recently found to generate presumed nitrenium ions, species which are generally considered as the ultimate mutagens/carcinogens derived from arylamines and nitroarenes. The primary photolysis products of arylazides, the arylnitrenes, can possibly react as electrophiles themselves, or they can be protonated and thus form the electrophilic nitrenium ions. Numerous arylazides and aryldiazides can be photoactivated to short-lived mutagens detectable in Salmonella typhimurium TA98. Structure-activity comparisons between arylazides and the matching arylamines and nitroarenes show correlations; e.g., phenyl azide and methyl-substituted phenyl azides are not mutagenic or only weakly mutagenic like aniline, nitrobenzene, and their methyl homologues, whereas 4-azidodiphenyl, 2-azidofluorene, 1-azidopyrene, azido-IQ, and azido-isoIQ are increasingly mutagenic in that order, like the matching amino and nitro compounds. It is hypothesized on the basis of these data that the nitrene/nitrenium ion is the reactive intermediate common to the three mutagenic pathways and that the reaction of the nitrene/nitrenium ion with DNA is rate limiting for the overall mutagenic process in Salmonella. The photochemical generation from arylazides of the reactive species, the nitrene/nitrenium ions, opens new perspectives for the understanding of the genotoxic activity of arylamines and nitroarenes in general and, specifically, of the food mutagens/carcinogens of the IQ type.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Dirr A., Wild D. Synthesis and mutagenic activity of nitro-imidazoarenes. A study on the mechanism of the genotoxicity of heterocyclic arylamines and nitroarenes. Mutagenesis. 1988 Mar;3(2):147–152. doi: 10.1093/mutage/3.2.147. [DOI] [PubMed] [Google Scholar]
- El-Bayoumy K., Lavoie E. J., Hecht S. S., Fow E. A., Hoffmann D. The influence of methyl substitution of the mutagenicity of nitronaphthalenes and nitrobiphenyls. Mutat Res. 1981 Apr;81(2):143–153. doi: 10.1016/0027-5107(81)90029-4. [DOI] [PubMed] [Google Scholar]
- Fuchs R. P., Bintz R. Activity of carcinogens that bind to the C8 position of guanine residues in an assay specific for the detection of -2 frameshift mutations in a defined hot spot. Environ Health Perspect. 1990 Aug;88:83–87. doi: 10.1289/ehp.908883. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heflich R. H., Unruh L. E., Thornton-Manning J. R., von Tungeln L. S., Fu P. P. Mutagenicity of 1-, 3- and 6-nitrosobenzo[a]pyrene in Salmonella typhimurium and Chinese hamster ovary cells. Mutat Res. 1989 Apr;225(4):157–163. doi: 10.1016/0165-7992(89)90113-9. [DOI] [PubMed] [Google Scholar]
- Later D. W., Pelroy R. A., Stewart D. L., McFall T., Booth G. M., Lee M. L., Tedjamulia M., Castle R. N. Microbial mutagenicity of isomeric two-, three-, and four-ring amino polycyclic aromatic hydrocarbons. Environ Mutagen. 1984;6(4):497–515. doi: 10.1002/em.2860060404. [DOI] [PubMed] [Google Scholar]
- Maron D. M., Ames B. N. Revised methods for the Salmonella mutagenicity test. Mutat Res. 1983 May;113(3-4):173–215. doi: 10.1016/0165-1161(83)90010-9. [DOI] [PubMed] [Google Scholar]
- Mermelstein R., Kiriazides D. K., Butler M., McCoy E. C., Rosenkranz H. S. The extraordinary mutagenicity of nitropyrenes in bacteria. Mutat Res. 1981 Jul;89(3):187–196. doi: 10.1016/0165-1218(81)90236-6. [DOI] [PubMed] [Google Scholar]
- Wild D., Dirr A., Fasshauer I., Henschler D. Photolysis of arylazides and generation of highly electrophilic DNA-binding and mutagenic intermediates. Carcinogenesis. 1989 Feb;10(2):335–341. doi: 10.1093/carcin/10.2.335. [DOI] [PubMed] [Google Scholar]
- Wild D., Dirr A. Mutagenic nitrenes/nitrenium ions from azido-imidazoarenes and their structure-activity relationships. Mutagenesis. 1989 Nov;4(6):446–452. doi: 10.1093/mutage/4.6.446. [DOI] [PubMed] [Google Scholar]
- Wild D., Dirr A. Synthesis of 2-azido-3-methylimidazo[4,5-f]quinoline and photolytic generation of a highly reactive and mutagenic IQ derivative. Carcinogenesis. 1988 May;9(5):869–871. doi: 10.1093/carcin/9.5.869. [DOI] [PubMed] [Google Scholar]