Genetic toxicology studies are performed early in a new chemical safety evaluation program to assess the potential for induction of genetic mutations or chromosomal damage. These studies are conducted in a tiered approach so that the toxicological relevance of any earlier observations can be assessed. In addition to standard genetic toxicology tests (In vitro Ames, Chromosomal aberration assay, Mouse lymphoma assay, In vivo rodent micronucleus assay, Comet assay, In vitro Micronucleus assay), Charles River also offers BlueScreen HC and μAmes.
BlueScreen HC Assay uses human derived p53-competent TK6 cells (GLuc-TO1) and exploits the proper regulation of the GADD45a gene using a luciferase reporter gene. GADD45a is particularly involved in response to genetic damage; expression can protect from genetic damage and deletion can increase susceptibility. The BlueScreen HC Assay detects direct acting mutagens, clastogens, aneugens, topoisomerase inhibitors and polymerase inhibitors.
The μAmes (miniaturized version of the standard Ames test) is conducted in 24-well plates using Salmonella typhimurium strains TA1535, TA97A, TA98, TA100 and Escherichia coli strain WP2 uvrA. The micro assay uses a high number of replicate vehicle control cultures/wells to enhance reliability of results. Compounds are tested in the presence and absence of metabolic activation (rat S9 mix). The plates are incubated for up to 72 h prior to colony counting.
Genotoxic potential (a positive result) is indicated where the compound causes a substantial dose-related increase in colony counts (at least two- or three-fold the spontaneous rate with colony counts outside the historical control range). The 24-well plates use a maximum dose of 750 μg per well, compared with 5000 μg per plate used in the standard assay. Since the study design is very similar to the standard Ames test, results of µAmes are highly predictive of the eventual GLP study.
Advantages
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Screening Tool: A number of candidate molecules can be screened simultaneously
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Low Test Item Usage: Testing can typically be performed using only 10 mg of test article
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Fast Results: BlueScreen data is available to the client within 72 h of dosing, μAmes within 96 h of dosing
For more information about our genetic toxicology services, contact us at 1.877.CRIVER.1 or askcharlesriver@crl.com.
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Genetic toxicology, genotoxic, chemical, chemicals, chemical development, chemical safety, genetic mutations, genetic mutation, chromosomal damage, Ames, chromosomal aberration, mouse lymphoma, mouse lymphoma assays, micronucleus, rodent micronucleus, assay, assays, Comet, in vivo, in vitro, BlueScreen HC, p53-competent, TK6 cells, GLuc-TO1, GADD45a gene, luciferase, luciferase reporter gene, GADD45a, mutagens, clastogens, aneugens, topoisomerase, polymerase, inhibitors, inhibitor, Salmonella typhimurium, Salmonella, S typhimurium, typhimurium, TA1535, TA97A, TA98, TA100, Escherichia coli, E coli, WP2 uvrA, rat S9
Genetic Toxicology Studies | Chemical Development | Charles River
Genetic toxicology studies are performed early in a new chemical safety evaluation program to assess the potential for induction of genetic mutations or chromosomal damage.