Bacterial Gene Mutations (Ames Assay)

These assays are designed for both GLP-compliant regulatory submission and non-GLP screening for product research and development. All GLP studies are in full compliance with GLP regulations, as deemed by the appropriate agency (FDA, EPA, OECD, EEC, JMHW and JMAFF). Non-GLP studies for discovery are conducted in the "spirit of GLP," including QA audit and inspection. All studies and proprietary information are strictly kept under confidential status at all times.

MUT-500: Plate Incorporation Assay

• 5 Strains: 4 Salmonella and E.coli WP2 uvrA (pKM101)
• With and without Exogenous Metabolic Activation
• Positive, negative, and sterility Controls
• Triplcate plating
• Non-GLP assay
• Time for completion: 4-6 weeks

MUT-501: Preincubation Assay

• 5 Strains: 4 Salmonella and E.coli WP2 uvrA (pKM101)
• With and without Exogenous Metabolic Activation
• Positive, negative, and sterility Controls
• Triplicate plating
• Non-GLP Assay
• Time for completion: 4-6 weeks

MUT-503: Plate Incorporation with Confirmatory (GLP) Assay

• 5 Strains: 4 Salmonella and E.coli WP2 uvrA (pKM101)
• With and without Exogenous Metabolic Activation
• Independent confirmatory trial (preincubation or plate incorporation)
• Positive, negative, and sterility Controls
• Triplicate plating
• Global compliance (GLP)
• Time for completion: 6-8 weeks
• Testing Article Required: Solids = 1-1.5g
  • Solids = 1-1.5g
  • Liquids = 3.5-5mL

High Throughput Salmonella/E. coli Screening Assays

• MUT-501: Spot Test
• MUT-502: Abbreviated Standard Assay
• MUT-503: Preincubation Screening Test
• MUT-504: Modified Standard Assay (nontoxic material)
• MUT-505: Modified Standard Assay (unknown toxicity)

Principles

Point mutations result from small changes in nucleotide sequence, including base-pair substitutions and frameshift mutations, some of which may be detected as changes in the conditions under which the mutant cell can grow. The bacterial mutation assay is most widely used to measure the ability of a test article to induce reverse mutations in selected histidine-requiring mutant strains of Salmonella typhimurium or tryptophan-requiring mutant strains of E. coli.

Limited Effectiveness of Bacterial Tests

There are circumstances where the performance of the bacterial reverse mutation test does not provide sufficient information for the assessment of genotoxicity. This may be the case for compounds that are highly toxic to bacteria (e.g. some antibiotics) and compounds thought or known to interfere with mammalian cell-specific systems (e.g. topoisomerase inhibitors, nucleoside analogs, or certain inhibitors of DNA metabolism). In these cases, usually two in vitro mammalian cell tests should be performed using two different cell types and two different endpoints.

Even when these additional tests are performed, it is still important to perform the bacterial reverse mutation test due to the high level of toxicity of the test chemical to bacteria. Some antibacterial agents, although highly toxic to the tester strains, are genotoxic at very low, sub-lethal concentrations in the bacterial reverse mutation test (e.g. nitrofuran antibiotics).