Induction of forward mutations at the thymidine kinase locus of mouse lymphoma cells: evidence for electrophilic and non-electrophilic mechanisms
Identifieur interne : 000B59 ( Istex/Curation ); précédent : 000B58; suivant : 000B60Induction of forward mutations at the thymidine kinase locus of mouse lymphoma cells: evidence for electrophilic and non-electrophilic mechanisms
Auteurs : B. Henry [États-Unis] ; S. G Grant [États-Unis] ; G. Klopman [États-Unis] ; H. S Rosenkranz [États-Unis]Source :
- Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis [ 0027-5107 ] ; 1998.
English descriptors
- Teeft :
- Active chemicals, Assay, Biological activity, Biophore, Biophores, C5ch, Carbon atom, Carcinogenesis, Carcinogenicity, Caspary, Cellular toxicity, Ch5ch, Chemical structure, Chemical structures, Chromosomal, Chromosomal aberrations, Chromosomal mechanisms, Chromosome, Chromosome loss, Chromosome missegregation, Concordance, Database, Dataset, Descriptor, Electrophilic, Environ, Experimental results, Inactivation, Inactive, Inactive chemicals, Inactive molecules, Induction, Informational content, Kinase, Klopman, Locus, Lower predictivity, Lumo, Lymphoma, Major biophores, Major multicase biophores, Mcgregor, Mechanistic, Mechanistic hypotheses, Micronucleus, Minor biophores, Modeling, Molecular events, Mouse lymphoma, Mouse lymphoma cells, Multicase, Multicase program, Multiple mechanisms, Mutagen, Mutagenesis, Mutagenic, Mutagenic events, Mutagenicity, Mutant, Mutation, Mutation assay, Mutation research, Mutational, Mutational events, National toxicology program, Oncogene, Oncogene activation, Other hand, Physical chemical properties, Point mutations, Predictive performance, Predictivity, Ring systems, Rodent, Rodent carcinogenicity, Rosenkranz, Salmonella, Salmonella model, Salmonella mutagenicity, Salmonella mutagenicity assay, Same chemicals, Sister chromatid exchanges, Somatic segregation, Structural basis, Subset, Suppressor, Thymidine, Thymidine kinase locus, Tkqrtky mouse lymphoma cell, Toxicity, Tubulin polymerization, Tumor suppressor gene, Unsupplemented, Vivo induction.
Abstract
Abstract: A database of 209 chemicals tested for induction of forward mutations at the heterozygous thymidine kinase (TK±) locus in L5178Y mouse lymphoma cells was analyzed for structure–activity relationships using the MultiCASE expert system. Consistent with evidence of several contributing biological mechanisms, these studies suggest that such mutations may occur by more than one mechanism. As might be expected, there was evidence for a component involving direct electrophilic attack on the cellular DNA, in a manner previously established as causative in the induction of mutations in Salmonella. In addition, however, there was also strong evidence for another mechanism or mechanisms involving chromosome missegregation, cellular toxicity or an alternate site of action, such as the microtubules.
Url:
DOI: 10.1016/S0027-5107(97)00231-5
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<front><div type="abstract" xml:lang="en">Abstract: A database of 209 chemicals tested for induction of forward mutations at the heterozygous thymidine kinase (TK±) locus in L5178Y mouse lymphoma cells was analyzed for structure–activity relationships using the MultiCASE expert system. Consistent with evidence of several contributing biological mechanisms, these studies suggest that such mutations may occur by more than one mechanism. As might be expected, there was evidence for a component involving direct electrophilic attack on the cellular DNA, in a manner previously established as causative in the induction of mutations in Salmonella. In addition, however, there was also strong evidence for another mechanism or mechanisms involving chromosome missegregation, cellular toxicity or an alternate site of action, such as the microtubules.</div>
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