Potentiation of the mutagenicity and recombinagenicity of bleomycin in yeast by unconventional intercalating agents
Identifieur interne : 001521 ( Main/Exploration ); précédent : 001520; suivant : 001522Potentiation of the mutagenicity and recombinagenicity of bleomycin in yeast by unconventional intercalating agents
Auteurs : George R. Hoffmann [États-Unis] ; Amanda M. Laterza [États-Unis] ; Katelyn E. Sylvia [États-Unis] ; Jason P. Tartaglione [États-Unis]Source :
- Environmental and Molecular Mutagenesis [ 0893-6692 ] ; 2011-03.
English descriptors
- Teeft :
- 3hobzp, Acridine, Acridines, Allele, Anova, Antimalarial, Arnone, Assay, Bleomycin, Bonferroni, Carcinogenesis, Cellsa, Cellsb, Cellsb convertants, Cerevisiae, Chem, Chinese hamster, Chinese hamster cells, Chloroquine, Classical intercalator, Classical intercalators, Comparisons tests, Computational, Convertant, Convertants, Diehl, Docking, Docking values, Enhancement, Environ, Ethanol, Frameshift, Frameshift mutations, Gene conversion, Genetic activity, Genotoxic, Genotoxic effects, Genotoxicity, Hamster, Hendry, Hoffmann, Ilv1, Intercalate, Intercalating, Intercalating agents, Intercalation, Intercalator, Intercalators, Locus, Metabolic activation, Micronucleus, Mitotic, Mitotic recombination, Modulator, Molecular mutagenesis, Mutagen, Mutagenesis, Mutagenic, Mutagenicity, Mutat, Mutation, National toxicology program, Nding, Noncovalent, Plate revertants, Plate trp1convertants, Plating, Point mutations, Potentiate, Potentiates, Potentiation, Povirk, Quinacrine, Recombinagenic, Recombination, Relative cell density ilv1 revertants, Reversion, Revertant frequencies, Revertants, Saccharomyces, Saccharomyces cerevisiae, Saccharomyces cerevisiae strain, Salmonella, Snyder, Strekowski, Stubbe, Tamoxifen, Toxicity, Toxicology, Trp1convertants, Trp5, Trp5 locus, Unconventional intercalators, Unfused, Unfused rings, Yeast, Yeast strain, Yepd, Zimmermann.
Abstract
Interactions between bleomycin (BLM) and conventional or unconventional intercalating agents were analyzed in an assay for mitotic gene conversion at the trp5 locus and reversion of the ilv1‐92 allele in Saccharomyces cerevisiae strain D7. BLM is a potent recombinagen and mutagen in the assay. Various chemicals modulate the genetic activity of BLM, producing either antimutagenic effects or enhanced genotoxicity. Effects of cationic amino compounds include enhancement of BLM activity by aminoacridines and protection against BLM by aliphatic amines. The potentiation of BLM is similar to findings in a micronucleus‐based BLM amplification assay in Chinese hamster V79 cells. In this study, the amplification of BLM activity was explored in yeast using known intercalators, compounds structurally related to known intercalators, and unconventional intercalators that were identified on the basis of computer modeling or results in the Chinese hamster BLM amplification assay. As shown in previous studies, the classical intercalator 9‐aminoacridine (9AA) caused dose‐dependent enhancement of BLM activity. Other compounds found to enhance the induction of mitotic recombination and point mutations in strain D7 were chlorpromazine, chloroquine, mefloquine, tamoxifen, diphenhydramine, benzophenone, and 3‐hydroxybenzophenone. The increased activity was detectable by cotreatment of yeast with BLM and the modulator compound in growth medium or by separate interaction of the intercalator with DNA followed by BLM treatment of nongrowing cells in buffer. The data support the interpretation drawn from micronucleus assays in mammalian cells that BLM enhancement results from DNA intercalation and may be useful in detecting noncovalent interactions with DNA. Environ. Mol. Mutagen. 52:130–144, 2011. © 2010 Wiley‐Liss, Inc.
Url:
DOI: 10.1002/em.20592
Affiliations:
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BLM is a potent recombinagen and mutagen in the assay. Various chemicals modulate the genetic activity of BLM, producing either antimutagenic effects or enhanced genotoxicity. Effects of cationic amino compounds include enhancement of BLM activity by aminoacridines and protection against BLM by aliphatic amines. The potentiation of BLM is similar to findings in a micronucleus‐based BLM amplification assay in Chinese hamster V79 cells. In this study, the amplification of BLM activity was explored in yeast using known intercalators, compounds structurally related to known intercalators, and unconventional intercalators that were identified on the basis of computer modeling or results in the Chinese hamster BLM amplification assay. As shown in previous studies, the classical intercalator 9‐aminoacridine (9AA) caused dose‐dependent enhancement of BLM activity. Other compounds found to enhance the induction of mitotic recombination and point mutations in strain D7 were chlorpromazine, chloroquine, mefloquine, tamoxifen, diphenhydramine, benzophenone, and 3‐hydroxybenzophenone. The increased activity was detectable by cotreatment of yeast with BLM and the modulator compound in growth medium or by separate interaction of the intercalator with DNA followed by BLM treatment of nongrowing cells in buffer. The data support the interpretation drawn from micronucleus assays in mammalian cells that BLM enhancement results from DNA intercalation and may be useful in detecting noncovalent interactions with DNA. Environ. Mol. Mutagen. 52:130–144, 2011. © 2010 Wiley‐Liss, Inc.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Massachusetts</li></region></list><tree><country name="États-Unis"><region name="Massachusetts"><name sortKey="Hoffmann, George R" sort="Hoffmann, George R" uniqKey="Hoffmann G" first="George R." last="Hoffmann">George R. Hoffmann</name></region><name sortKey="Hoffmann, George R" sort="Hoffmann, George R" uniqKey="Hoffmann G" first="George R." last="Hoffmann">George R. Hoffmann</name><name sortKey="Hoffmann, George R" sort="Hoffmann, George R" uniqKey="Hoffmann G" first="George R." last="Hoffmann">George R. Hoffmann</name><name sortKey="Laterza, Amanda M" sort="Laterza, Amanda M" uniqKey="Laterza A" first="Amanda M." last="Laterza">Amanda M. Laterza</name><name sortKey="Sylvia, Katelyn E" sort="Sylvia, Katelyn E" uniqKey="Sylvia K" first="Katelyn E." last="Sylvia">Katelyn E. Sylvia</name><name sortKey="Tartaglione, Jason P" sort="Tartaglione, Jason P" uniqKey="Tartaglione J" first="Jason P." last="Tartaglione">Jason P. Tartaglione</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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