Mutagenic activity of arylnitrenium ions from arylazides--induction of sister chromatid exchange in mammalian (V79 Chinese hamster) cells. 1992

D Wild
Institute of Pharmacology and Toxicology, University of Würzburg, Germany.

Photolysis of arylazides produces short-lived reactive species, very likely arylnitrenium ions which bind to nucleotides and DNA and produce mutations in Salmonella. The present report shows that arylazides can be photo-activated in mammalian (V79 Chinese hamster) cells and that sister chromatid exchange can thus be induced. Arylazides studied are (in order of decreasing SCE-inducing potency) azido-isoIQ, azido-MeIQ, azido-IQ, azido-MeIQx, azido-PhIP, 6-azido-chrysene, 2-azidofluorene, 4-azidofluorene, 2-azido-naphthalene, 4-azidobi-phenyl, 2-azidobiphenyl, 2,4,6-trimethylphenylazide, phenylazide (inactive). The structure-activity relationships emerging from the data are the same as those found previously in Salmonella. In line with this, a clearcut positive linear correlation was seen between the logarithm of the SCE-inducing potency in V79 cells and the logarithm of the mutagenic potency in Salmonella (r = 0.955). Therefore, the ultimate reactive species derived from IQ and related heterocyclic aromatic amines are extremely potent genotoxins, not only in a bacterial but also in a mammalian cell. Previous findings of only weak genotoxic activity of IQ and related food mutagens in certain cultured mammalian cells must therefore be reinterpreted as the result of an insufficient activation of these amines in the cells used, possibly because of insufficient acetylation competence.

UI MeSH Term Description Entries
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003412 Cricetulus A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research. Hamsters, Armenian,Hamsters, Chinese,Hamsters, Grey,Armenian Hamster,Armenian Hamsters,Chinese Hamster,Chinese Hamsters,Grey Hamster,Grey Hamsters,Hamster, Armenian,Hamster, Chinese,Hamster, Grey
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004307 Dose-Response Relationship, Radiation The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation. Dose Response Relationship, Radiation,Dose-Response Relationships, Radiation,Radiation Dose-Response Relationship,Radiation Dose-Response Relationships,Relationship, Radiation Dose-Response,Relationships, Radiation Dose-Response
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D005609 Free Radicals Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. Free radicals include reactive oxygen and nitrogen species (RONS). They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Free Radical
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001386 Azides Organic or inorganic compounds that contain the -N3 group. Azide

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