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The Ames test is a widely employed method that uses bacteria to test whether a given chemical can cause mutations in the DNA of the test organism. More formally, it is a biological assay to assess the mutagenic potential of chemical compounds. A positive test indicates that the chemical is mutagenic and therefore may act as a carcinogen, because cancer is often linked to mutation. The test serves as a quick and convenient assay to estimate the carcinogenic potential of a compound because standard carcinogen assays on mice and rats are time-consuming and expensive. However, false-positives and false-negatives are known.
Mutagenesis is a process by which the genetic information of an organism is changed by the production of a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using laboratory procedures. A mutagen is a mutation-causing agent, be it chemical or physical, which results in an increased rate of mutations in an organism's genetic code. In nature mutagenesis can lead to cancer and various heritable diseases, and it is also a driving force of evolution. Mutagenesis as a science was developed based on work done by Hermann Muller, Charlotte Auerbach and J. M. Robson in the first half of the 20th century.
In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in animals, such mutagens can therefore be carcinogens, although not all necessarily are. All mutagens have characteristic mutational signatures with some chemicals becoming mutagenic through cellular processes.
Toxicology is a scientific discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating exposures to toxins and toxicants. The relationship between dose and its effects on the exposed organism is of high significance in toxicology. Factors that influence chemical toxicity include the dosage, duration of exposure, route of exposure, species, age, sex, and environment. Toxicologists are experts on poisons and poisoning. There is a movement for evidence-based toxicology as part of the larger movement towards evidence-based practices. Toxicology is currently contributing to the field of cancer research, since some toxins can be used as drugs for killing tumor cells. One prime example of this is ribosome-inactivating proteins, tested in the treatment of leukemia.
ENU, also known as N-ethyl-N-nitrosourea (chemical formula C3H7N3O2), is a highly potent mutagen. For a given gene in mice, ENU can induce 1 new mutation in every 700 loci. It is also toxic at high doses.
Genotoxicity is the property of chemical agents that damage the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with mutagenicity, all mutagens are genotoxic, but some genotoxic substances are not mutagenic. The alteration can have direct or indirect effects on the DNA: the induction of mutations, mistimed event activation, and direct DNA damage leading to mutations. The permanent, heritable changes can affect either somatic cells of the organism or germ cells to be passed on to future generations. Cells prevent expression of the genotoxic mutation by either DNA repair or apoptosis; however, the damage may not always be fixed leading to mutagenesis.
Auxotrophy is the inability of an organism to synthesize a particular organic compound required for its growth. An auxotroph is an organism that displays this characteristic; auxotrophic is the corresponding adjective. Auxotrophy is the opposite of prototrophy, which is characterized by the ability to synthesize all the compounds needed for growth.
Bruce Nathan Ames is an American biochemist. He is a professor of Biochemistry and Molecular Biology Emeritus at the University of California, Berkeley, and was a senior scientist at Children's Hospital Oakland Research Institute (CHORI). He is the inventor of the Ames test, a system for easily and cheaply testing the mutagenicity of compounds.
Toxicogenomics is a subdiscipline of pharmacology that deals with the collection, interpretation, and storage of information about gene and protein activity within a particular cell or tissue of an organism in response to exposure to toxic substances. Toxicogenomics combines toxicology with genomics or other high-throughput molecular profiling technologies such as transcriptomics, proteomics and metabolomics. Toxicogenomics endeavors to elucidate the molecular mechanisms evolved in the expression of toxicity, and to derive molecular expression patterns that predict toxicity or the genetic susceptibility to it.
Ethyl methanesulfonate (EMS) is a mutagenic, teratogenic, and carcinogenic organic compound with formula C3H8SO3. It produces random mutations in genetic material by nucleotide substitution; particularly through G:C to A:T transitions induced by guanine alkylation. EMS typically produces only point mutations. Due to its potency and well understood mutational spectrum, EMS is the most commonly used chemical mutagen in experimental genetics. Mutations induced by EMS exposure can then be studied in genetic screens or other assays.
Graham Charles Walker is an American biologist, notable for his work explicating the structure and function of proteins involved in DNA repair and mutagenesis, with applications for cancer, and for understanding rhizobium (bacterial) functions that infect plants and mammals.
Methylnitronitrosoguanidine (MNNG or MNG, NTG when referred to colloquially as nitrosoguanidine) is a biochemical tool used experimentally as a carcinogen and mutagen. It acts by adding alkyl groups to the O6 of guanine and O4 of thymine, which can lead to transition mutations between GC and AT. These changes do not cause a heavy distortion in the double helix of DNA and thus are hard to detect by the DNA mismatch repair system.
The Hazardous Substances Data Bank (HSDB) was a toxicology database on the U.S. National Library of Medicine's (NLM) Toxicology Data Network (TOXNET). It focused on the toxicology of potentially hazardous chemicals, and included information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, and related areas. All data were referenced and derived from a core set of books, government documents, technical reports, and selected primary journal literature. Prior to 2020, all entries were peer-reviewed by a Scientific Review Panel (SRP), members of which represented a spectrum of professions and interests. Last Chairs of the SRP are Dr. Marcel J. Cassavant, MD, Toxicology Group, and Dr. Roland Everett Langford, PhD, Environmental Fate Group. The SRP was terminated due to budget cuts and realignment of the NLM.
John W. Drake (1932-2020) was an American microbiologist and geneticist, working for over half a century in the field of mutagenesis and DNA repair.
Wang Aiping is a Chinese pharmacologist and toxicologist. For over 20 years, Wang has researched drug and toxicity testing and has experience in new drug development. Since 2001, he has been Director of Drug Safety Evaluation and Research at the Academy of Medical Sciences, Peking Union Medical College and was also made General Manager of Technological development at Peking Union Medical College's Jianhao Pharmaceutical Technology Development Co., Ltd.
Antimutagens are the agents that interfere with the mutagenicity of a substance. The interference can be in the form of prevention of the transformation of a promutagenic compound into actual active mutagen, inactivation, or otherwise the prevention of Mutagen-DNA reaction.
Rajani A. Bhisey is an Indian scientist. She specializes in the field of environmental carcinogenesis and molecular epidemiology of cancer, occupational hazards.
Gareth Jenkins is a professor of molecular carcinogenesis at Swansea University Medical School. Based in the Institute of Life Science, his interests include the study of DNA mutation induction and the role of DNA mutations as diagnostic biomarkers for cancer. He is also director of research of the medical school and a “research leader” for Health and Care Research Wales. Jenkins' research gained much recognition during 2016 when his revolutionary cancer-detecting blood test was widely covered in the British press.
The somatic mutation and recombination tests (SMARTs) are in vivo genotoxicity tests performed in Drosophila melanogaster (Fruit fly). These fruit fly tests are a short-term test and a non-mammalian approach for in vivo testing of putative genotoxins found in the environment. D. melanogaster has a short lifespan, which allows for fast reproductive cycles and high-throughput genotoxicity testing. D. melanogaster also has around 75% functional orthologs of human disease-related genes, making it an attractive in vivo model for human research. The tests identify loss of heterozygosity for the specified genetic markers in heterozygous or trans-heterozygous adults using phenotypically observable genetic markers in adult tissues. Although diverse events like point mutations/deletions, nondisjunction, and homologous mitotic recombination might theoretically cause this loss of heterozygosity, nondisjunction processes are generally not relevant for most of the examined chemicals. SMARTs are two different tests that use the same genetic foundation, but target different adult tissues and are named accordingly: the wing-spot test and the eye-spot test.
Sheldon Wolff was an American radiobiologist, cytogeneticist, and environmental health expert on mutagenic chemicals.
References
- 1 2 3 4 5 "Environmental Mutagen Society web site". Archived from the original on 16 April 2011. Retrieved 12 December 2010.
- ↑ Shelby, Michael D. (December 1978). "EMIC: A Centralized Source of Chemical Mutagenesis Information". Environmental Health Perspectives. Brogan & Partners. 27: 21–25. doi:10.1289/ehp.782721. JSTOR 3428858. PMC 1637307 . PMID 738236.
- ↑ "Genetic Toxicology Data Bank (GENE-TOX) - Peer-reviewed genetic toxicology test data for over 3,000 chemicals". US National Library of Medicine.
- ↑ "Environmental Mutagenic Hazards". Science. 187 (4176): 503–514. February 14, 1975. Bibcode:1975Sci...187..503.. doi:10.1126/science.163482. PMID 163482.
- ↑ Ames, Bruce N. (1971). "The Detection of Chemical Mutagens with Enteric Bacteria" (PDF). In Alexander Hollaender (ed.). Chemical Mutagens. pp. 267–282. doi:10.1007/978-1-4615-8966-2_9. ISBN 978-1-4615-8968-6.
{{cite book}}:|journal=ignored (help) - ↑ "EMS Meetings" . Retrieved 30 January 2023.
- ↑ "EMS: Awards and Honors" . Retrieved 13 December 2010.
