Eukaryotic mutation tests

Related Tests. Many tests related to the two types of eukaryote-mutation tests are discussed earlier in this section, and many of them are simply variations of the tests described. Two distinct classes are worthy of mention the first uses yeasts as the test organisms, and the second is the spot test for mutations in mice. 

Gene mutation tests in a eukaryotic system in vitro, e.g. the Hypoxanthine - guanine - phosphoribosyl - transferase (HGPRT) gene mutation tests in hamster cells. 

Mutagenicity tests are usually carried out in vitro and in vivo, often using both prokaryotic and eukaryotic organisms. A well-known example is the Ames test, which assesses the ability of a drug to induce mutation reversions in E. coli and Salmonella typhimurium. 

Following the first demonstration of the deleterious effect of radiation and ultimately that of chemicals on genetic material, numerous test systems have been used to study the induction of DNA damage, chromosomal aberrations, and mutations. This broad spectrum of activity resulted in the birth of genetic toxicology. The test organisms include prokaryotes (e.g., bacteria, fungi) and eukaryotes (e.g., yeast, fruit flies, plants, mammals). 

Genotoxic Effects. 1,2-Dibromoethane has been tested extensively to assess its genotoxic potential in prokaryotic, eukaryotic, and mammalian systems. Tables 2-7 and 2-8 present the results of in vivo and in vitro genotoxicity studies, respectively. The results of these studies indicate that 1,2-dibromoethane is a potent mutagen, producing a broad spectrum of mutations in various test systems. 

The test is used to detect gene mutation in yeast, a eukaryotic microorganism. 

The test is used to detect forward and reverse gene mutation in Aspergillus nidulans, a eukaryotic fungus. These mutations are detected by changes in colonial morphology or nutritional requirements in treated populations. The methionine and 2-thioxanthine forward mutation systems can be used to detect mutations in Aspergillus nidulans. 

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. 

One system uses mouse lymphoma cells and detects mutations that cause deficiency of thymidine kinase (TK). Another uses Chinese hamster cells and detects mutations in the gene that produces hypoxanthine-guanine phosphoribosyl transferase (HGPRT). Both tests cure efficient, are widely applied, and can be completed in a few weeks. Although not as simple, rapid, and efficient as the Salmonella tests, they have the advantage of being done in a eukaryote. Mammalian-cell cultures cure also used to test for chromosomal mutation. 

Microbial tests based on reverse mutation are specific, because a unique mutation must undergo precise reversion.423 This may be a limitation, in that only one genetic end point is monitored, although little empirical evidence supports this criticism. A prokaryotic or eukaryotic cell apparently uses a number of pathways at the same time to cope with adducts that cure covalently bound to DMA. 

As indicated in Table 2-4, 2-nitrophenol did not increase the frequency of reverse mutations in Salmonella typhimurium or in Escherichia coli in the presence or absence of metabolic activation, nor did it induce DNA damage when tested in Bacillus subtilis. No data were available regarding genotoxic properties of 2-nitrophenol in eukaryotic organisms. 

A number of short-term tests can be used to determine the genotoxic potential of chemicals. These tests use both prokaryotic and eukaryotic cells and measure such end points as gene mutations, chromosomal aberrations, and interactions with critical macromolecules It is widely recognized chat no test can detect all genotoxic compounds, and multiple end points are required to provide a reliable assessment of genotoxiclty. Information from several tests can be combined to reveal two important toxic effects carcinogenesis and mutagenesis. 

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