Mutation mutagenicity

Mutation Mutagenic responses mutations/locus/ gamete mutations/locus/ survivor... 

Some materials cause genetic changes that can cause cancer (carcinogen), mutation (mutagens), and birth defects (teratogens). These effects are often hard to document due to latency periods and synergisms. 

A PRIMER ON GENETICS, MUTATION, MUTAGENS, AND THE IMPLICATIONS OF MUTAGENESIS... 

Food products contain thousands of compounds — some of nutritive value — nonnutritive components, numerous additives, substances formed during processing, and pesticide residues. Their safety is of utmost importance for human health protection, including cancer risk assessment. In order to evaluate the carcinogenicity of individual food constituents and their mixtures, often of unknown chemical structure, as well as the impact of cooking procedures, short-term reliable and inexpensive tests are necessary. Since cancer risk associated with chemical compounds is thought to stem mainly from their ability to induce mutations, mutagenicity... 

It is for instance well known, or at least well inferred, that radiation and many chemicals are a more or less direct cause of genetic aberrations, and the aberrant entity may in turn be called an oncogene, as previously noted. Industrial chemicals in particular are routinely tested and screened for carcinogenicity, notably for their ability to produce bacterial mutations (mutagenicity) by what is usually called the Ames test... 

The Nature of Mutations The Results of Mutations Mutagens and Carcinogens... 

Mutagenic pertaining to an agent that causes genetic mutations Mutagenicity property of an element, a compound or a substance to cause mutations... 

Interest ia the toxicity of aldehydes has focused primarily on specific compounds, particularly formaldehyde, acetaldehyde, and acroleia (13). Litde evidence exists to suggest that occupational levels of exposure to aldehydes would result ia mutations, although some aldehydes are clearly mutagenic ia some test systems. There are, however, acute effects of aldehydes. 

Fig. 9. Mutagenesis by a synthetic oligonucleotide of a cloned sequence available in single-stranded form (a) single-stranded M13 template containing uracil (U) residues (b) double-stranded product, uracil residues are not mutagenic (c) strong selection for M13 phages containing mutation of interest (23).

It is possible to make a number of mutations in a small sequence by synthesizing the mutagenic oligonucleotide with a small amount of incorrect nucleotide at each position, such that each oligonucleotide contains an average of one or two incorrect bases. This is the so-called dirty botde synthesis. 

Mutagenicity. The AJ-nitrosamines, in general, induce mutations in standard bacterial-tester strains (117). As with carcinogenicity, enzymatic activation, typically with Hver microsomal preparations, is required. Certain substituted A/-nitrosamine derivatives (12) induce mutations without microsomal activation (31,33,34). Because the a-acetoxy derivatives can hydroly2e to the corresponding a-hydroxy compounds, this is consistent with the hypothesis that enzymatic oxidation leads to the formation of such unstable a-hydroxy intermediates (13) (118). However, for simple /V-nitrosamines, no systematic relationship has been found between carcinogenicity and mutagenicity (117,119—123). 

Literature reports iadicate that sodium sorbate causes weak genotoxic effects such as chromosomal aberrations and mutations ia mammalian cells (172,173). This effect is thought to be caused by oxidative products of sodium sorbate ia stored solutions (173—175). The main oxidation product of sodium sorbate, 4,5-oxohexenoate, is mutagenic ia a Salmonella mammahan-microsome test (176). Sorbic acid and potassium sorbate were not genotoxic under the same test procedures (167,172,174—177). 

The choice of the strain of microorganism is one of the important variables in the process. The strains to be used in manufacture are mutants of the original producer, which are chosen as the result of a planned program of mutant selection. Sometimes a spontaneous mutation occurs usually, it is induced by mutagenic agents or irradiation of various sorts. The choice of the best strain depends on its abiUty to produce large amounts of the proper antibiotic in a reasonable time from ingredients that are economically feasible (73). 

Sodium chlorite is not Hsted by the USEPA or any regulatory authority as a carcinogen. Studies conducted ia mice and rats did not show an increase in tumors in animals exposed to sodium chlorite in thek drinking water. Sodium chlorite has been found to have mutagenic activity in some in vitro test systems such as the Ames Salmonella reverse mutation assay without the presence of metaboHc activators. The significance of these test results in regard to human health is not clear because of the oxidizing effects of the chlorite ion (149). 

Physicochemical properties requked include melting/boiling point, vapor pressure, solubiUty, and flammabiUty/explosion characteristics. The toxicological studies include acute toxicity tests, oral, inhalation, and dermal skin and eye kritation skin sensiti2ation subacute toxicity, oral, inhalation, and dermal and mutagenicity tests. In vitro reverse mutation assay (Ames test) on Salmonella typhimurium and/or E.scherichia coli and mammalian cytogenic test. In vivo mouse micronucleus test. 

Ethylene oxide has been shown to produce mutagenic and cytogenic effects in a variety of test systems (226). An increased frequency of chromosomal aberrations in peripheral lymphocytes of monkey exposed to ethylene oxide for 104 weeks has been reported (240). In mice, it is an effective inducer of chromosome breaks leading to dominant-lethal mutations. In addition, ethylene oxide has been shown to induce heritable effects in the heritable translocation test conducted in mice exposed to ethylene oxide by inhalation (241,242). In this study, male mice were exposed to ethylene oxide ranging from 165 to 300 ppm for 6 h per day 5 or 7 days/week for 8.5 weeks. Ethylene oxide has also been shown to bind to proteins (243) as well as to DNA (244). Several studies on ethylene oxide-exposed workers have demonstrated an increased incidence of chromosomal aberrations and sister chromatid exchanges the relevance of such effects to human health evaluation is currendy uncertain. 

MUTAGEN A chemical or physical agent that can cause a change (mutation) in the genetic material of a living cell. 

A mutagen is a chemical that can induce alterations in the DNA. Mutations occurring in germ cells are inheritable and may lead to genetic diseases. If mutations take place in somatic cells, carcinogenesis may be initiated. 

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