Ames test, gene mutations

Fertility and early embryonic development rats Developmental rats, rabbits Prenatal and postnatal development rats Genetic toxicology Ames test, gene mutations in mammalian cells grown in vitro (mouse L5178Y cells), and chromosomal damage in intact animals (bone marrow cells in rats)... 

Bacterial reverse mutation test Ames Test Gene mutations Basepair substitution, addition or deletion... 

S typhimurium TA 98, TA 100 (Ames test) Gene mutation No data + Takahashi et al. 1985... 

Propofol Tests for mutagenicity included the Ames mutation test, gene mutation/gene conversion using Saccharomyces cerevisiae, in vitro cytogenetic studies in Chinese hamsters, and a mouse micronucleus test. None of these have shown mutagenic potential. 

Bacterial mutagenicity Ames Salmonella) test Gene mutations 471 870.5100... 

Surfactant Acute toxicity Irritation to skin" (rabbit) Irritation to eye (rabbit) Sensitization (Magnusson-Kligman test) Gene mutation (Ames test) NOAEL ... 

The mutagenic potential of diisopropyl methylphosphonate was investigated using the Ames assay. The compound was obtained from two different sources and tested on Salmonella typhimurium strains TA-1535, TA-1537, TA-1538, TA-98, and TA-100, both with and without S-9 activation. The compound did not demonstrate mutagenic activity in any of the assays (Hart 1980). Diisopropyl methylphosphonate was also negative for gene mutation in Saccharomyces cerevisiae (Hart 1980). 

The Ames Salmonella typhimurium microsome reverse mutation test (ability to produce point gene mutations of a base pair). 

Assays for Gene Mutations Salmonella Typhimurium reverse mutation assay (Ames test, / ... 

The bacterial and mammalian cell assays for gene mutation were developed to measure statistically significant increases in the numbers of mutant colonies derived from rare events many millions of exposed cells must be plated out to allow the assessment of mutation frequency. The Salmonella typhimurium reverse mutation assay ( Ames test) is carried out in a variety of different mutant strains selected to identify the various classes of mutation. The test generates many hundreds of Petri dishes for counting and is not practical for profiling. 

The use of yeast cells as a eukaryotic complement to the Ames test led to the development of several protocols for the detection of mutation, gene conversion and recombination. The formal introduction of methods [23] followed by much development work from Zimmermarm s laboratory led to large systematic studies [24, 25] and OECD guidelines for the test battery (OECD 480, 481). However the assays are now rarely used, at least in part because of concerns over low sensitivity, thought to reflect limited permeability of the cell wall. 

Safety of Enterosgel preparation in terms of mutagenic action has been shown in the tests for induction of chromosome aberrations in bone marrow cells, in cultured human peripheral blood lymphocytes, and in the Ames test for induction of reversible gene mutations in Salmonella typhimurium. 

In general, genotoxicity standard assays (e.g., bacterial reverse mutation assay [Ames test], in vitro chromosomal aberration assay, mouse lymphoma gene mutation assay, and rodent micronucleus assay) may not be suitable assays because the test cells do not contain the appropriate receptors to transport the product (i.e.,not a relevant species) or because the biopharmaceutical... 

Twenty-seven out of 44 FDA-approved biopharmaceuticals have been tested in a battery of genotoxicity assays. Eighty-five different assays performed yielded negative results. The most commonly performed assays were the Ames test, the chromosomal aberration assay in human lymphocytes, the mouse lymphoma gene mutation assay, and the mammalian in vivo erythrocyte micronucleus test. Examples of the range of biopharmaceutical products tested include, domase alfa (deoxyribonuclease I-DNAse), trastuzumab (mAb to human epidermal growth factor receptor 2), alteplase (tissue plasminogen activator), infliximab (mAb to the human tumor necrosis factor a). 

There was no evidence of genotoxicity in the standard genotoxicity test battery bacteria reverse mutation (Ames) tests, forward gene mutations in mammalian (Chinese hamster ovary AS42) cells, or mouse bone marrow MN test... 

Prenatal and postnatal development none Genetic toxicology0 Ames test, human lymphocyte chromosomal aberration assay, CHO/HGPRT gene mutation assay, mouse micronucleus assay Carcinogenicity none... 

Developmental rats, rabbits Prenatal and postnatal development rats Genetic toxicology Ames tests, mouse lymphoma cell forward gene mutation test, human peripheral blood lymphocyte chromosome aberration test, in vivo micronucleus test in mice and ex vivo UDS test in rat liver hepatocytes... 

The bacterial reverse mutation test (Ames Test) investigates the ability of chemicals and drags to induce reverse (back) mutations in bacteria, which involves base pair substitutions additions and/or deletions (frameshift mutations) of one or a few DNA base pairs. The bacterial strains used in the test system have mutations in genes coding for enzymes required for the biosynthesis of the amino acids histidine (Salmonella typhimurium) and tryptophan (Escherichia coli). If... 

Negative results have been reported in vitro from Ames, cytogenetics, and gene mutation tests reported in the secondary literature. There are no in vivo data available. These data do not support classification. 

Phosphine has been reported as negative for induction of reverse gene mutations up to cytotoxic doses in the Ames assay Salmonella typhimurium). Increased chromosomal aberrations were reported in Chinese hamster ovary (CHO) cells exposed to 2500 and 5000 ppm of phosphine without activation with the S9 fraction. Chromosomal aberrations in CHOs were also reported in cells tested with S9 activation at 2500 ppm, but not 5000 ppm. 

The Ames test allows one to test the ability of a substance to interfere with DNA, which has the information necessary for expression of specific proteins. This information is encoded by the sequence of base pairs in the DNA molecule, with triplets of base pairs (mRNA codons) encoding for a specific amino acid in the sequence of a protein. Ames system focuses on the fact that mutations in oncogenes and tumor suppressor genes of somatic cells can be involved in tumor formation. 

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