Which is Considered a Chemical Mutagen

Physical or chemical agent that increases the rate of genetic mutation

In genetics, a
mutagen
is a concrete or chemic agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations in a higher place the natural background level. As many mutations tin can cause cancer in animals, such mutagens can therefore exist carcinogens, although not all necessarily are. All mutagens accept feature mutational signatures with some chemicals becoming mutagenic through cellular processes.

The process of Deoxyribonucleic acid condign modified is called mutagenesis. Not all mutations are acquired by mutagens: so-chosen “spontaneous mutations” occur due to spontaneous hydrolysis, errors in Deoxyribonucleic acid replication, repair and recombination.

Discovery

[edit]

The get-go mutagens to be identified were carcinogens, substances that were shown to exist linked to cancer. Tumors were described more than two,000 years earlier the discovery of chromosomes and DNA; in 500 B.C., the Greek doctor Hippocrates named tumors resembling a crab
karkinos
(from which the word “cancer” is derived via Latin), meaning crab.[one]
In 1567, Swiss physician Paracelsus suggested that an unidentified substance in mined ore (identified equally radon gas in modernistic times) caused a wasting disease in miners,[2]
and in England, in 1761, John Hill made the start directly link of cancer to chemical substances by noting that excessive use of snuff may crusade nasal cancer.[3]
In 1775, Sir Percivall Pott wrote a paper on the high incidence of scrotal cancer in chimney sweeps, and suggested chimney soot as the crusade of scrotal cancer.[4]
In 1915, Yamagawa and Ichikawa showed that repeated application of coal tar to rabbit’s ears produced cancerous cancer.[5]
Afterward, in the 1930s the carcinogen component in coal tar was identified as a polyaromatic hydrocarbon (PAH), benzo[a]pyrene.[2]
[vi]
Polyaromatic hydrocarbons are also present in soot, which was suggested to be a causative agent of cancer over 150 years earlier.

The association of exposure to radiation and cancer had been observed every bit early on equally 1902, six years after the discovery of X-ray by Wilhelm Röntgen and radioactive decay past Henri Becquerel.[7]
Georgii Nadson and High german Filippov were the starting time who created fungi mutants under ionizing radiations in 1925.[eight]
[nine]
The mutagenic property of mutagens was first demonstrated in 1927, when Hermann Muller discovered that x-rays tin cause genetic mutations in fruit flies, producing phenotypic mutants too as observable changes to the chromosomes,[10]
[11]
visible due to the presence of enlarged “polytene” chromosomes in fruit fly salivary glands.[12]
His collaborator Edgar Altenburg also demonstrated the mutational effect of UV radiation in 1928.[13]
Muller went on to employ x-rays to create Drosophila mutants that he used in his studies of genetics.[fourteen]
He likewise institute that X-rays not but mutate genes in fruit flies,[10]
but also have furnishings on the genetic makeup of humans.[15]
[
ameliorate source needed
]

Like work by Lewis Stadler besides showed the mutational effect of 10-rays on barley in 1928,[16]
and ultraviolet (UV) radiation on maize in 1936.[17]
The effect of sunlight had previously been noted in the nineteenth century where rural outdoor workers and sailors were found to be more than prone to skin cancer.[18]

Chemical mutagens were non demonstrated to cause mutation until the 1940s, when Charlotte Auerbach and J. Yard. Robson found that mustard gas can cause mutations in fruit flies.[19]
A large number of chemical mutagens accept since been identified, especially after the evolution of the Ames exam in the 1970s by Bruce Ames that screens for mutagens and allows for preliminary identification of carcinogens.[twenty]
[21]
Early studies by Ames showed around ninety% of known carcinogens can be identified in Ames test as mutagenic (later studies however gave lower figures),[22]
[23]
[24]
and ~fourscore% of the mutagens identified through Ames test may also be carcinogens.[24]
[25]
Mutagens are not necessarily carcinogens, and vice versa. Sodium azide for example may be mutagenic (and highly toxic), but it has non been shown to be carcinogenic.[26]

Furnishings

[edit]

Mutagens can cause changes to the Deoxyribonucleic acid and are therefore genotoxic. They can affect the transcription and replication of the DNA, which in severe cases tin pb to cell expiry. The mutagen produces mutations in the DNA, and deleterious mutation can result in aberrant, impaired or loss of function for a particular factor, and accumulation of mutations may pb to cancer. Mutagens may therefore be also carcinogens. Withal, some mutagens exert their mutagenic event through their metabolites, and therefore whether such mutagens really become carcinogenic may be dependent on the metabolic processes of an organism, and a chemical compound shown to exist mutagenic in 1 organism may non necessarily be carcinogenic in another.[27]

Different mutagens act on Dna differently. Powerful mutagens may result in chromosomal instability,[28]
causing chromosomal breakages and rearrangement of the chromosomes such as translocation, deletion, and inversion. Such mutagens are called clastogens.

Mutagens may also modify the DNA sequence; the changes in nucleic acid sequences by mutations include substitution of nucleotide base of operations-pairs and insertions and deletions of ane or more nucleotides in DNA sequences. Although some of these mutations are lethal or cause serious disease, many have small-scale furnishings as they exercise not result in residue changes that have significant event on the structure and office of the proteins. Many mutations are silent mutations, causing no visible effects at all, either because they occur in non-coding or non-functional sequences, or they practise non alter the amino-acid sequence due to the redundancy of codons.[
citation needed
]

Some mutagens tin cause aneuploidy and change the number of chromosomes in the cell. They are known every bit aneuploidogens.[29]

In Ames test, where the varying concentrations of the chemical are used in the test, the dose response bend obtained is well-nigh always linear, suggesting that there may be no threshold for mutagenesis. Similar results are also obtained in studies with radiation, indicating that there may be no safe threshold for mutagens. Still, the no-threshold model is disputed with some arguing for a dose rate dependent threshold for mutagenesis.[xxx]
[ten]
Some have proposed that low level of some mutagens may stimulate the Deoxyribonucleic acid repair processes and therefore may non necessarily be harmful. More than recent approaches with sensitive analytical methods have shown that there may exist non-linear or bilinear dose-responses for genotoxic effects, and that the activation of Deoxyribonucleic acid repair pathways tin prevent the occurrence of mutation arising from a low dose of mutagen.[31]

Types

[edit]

Mutagens may exist of physical, chemical or biological origin. They may act directly on the DNA, causing direct damage to the Dna, and most ofttimes result in replication fault. Some however may deed on the replication machinery and chromosomal partition. Many mutagens are non mutagenic by themselves, only tin can form mutagenic metabolites through cellular processes, for example through the activeness of the cytochrome P450 system and other oxygenases such as cyclooxygenase.[32]
Such mutagens are chosen promutagens.[33]

Concrete mutagens

[edit]

  • Ionizing radiations such as X-rays, gamma rays and blastoff particles cause DNA breakage and other amercement. The near common lab sources include cobalt-sixty and cesium-137.
  • Ultraviolet radiations with wavelength above 260 nm are absorbed strongly by bases, producing pyrimidine dimers, which tin can cause error in replication if left uncorrected.
  • Radioactivity, such every bit
    fourteenC in DNA which decays into nitrogen.

Deoxyribonucleic acid reactive chemicals

[edit]

A big number of chemicals may interact straight with DNA. Nevertheless, many such as PAHs, aromatic amines, benzene are not necessarily mutagenic by themselves, just through metabolic processes in cells they produce mutagenic compounds.[
commendation needed
]

  • Reactive oxygen species (ROS) – These may be superoxide, hydroxyl radicals and hydrogen peroxide, and large number of these highly reactive species are generated past normal cellular processes, for example every bit a past-products of mitochondrial electron transport, or lipid peroxidation. Equally an example of the latter, 15-hydroperoxyicosatetraenocic acrid, a natural product of cellular cyclooxygenases and lipoxygenases, breaks down to class four-hydroxy-2(E)-nonenal, 4-hydroperoxy-ii(E)-nonenal, 4-oxo-two(E)-nonenal, and
    cis-4,5-epoxy-ii(E)-decanal; these bifunctional electophils are mutagenic in mammalian cells and may contribute to the development and/or progression of human cancers (see xv-Hydroxyicosatetraenoic acid).[34]
    A number of mutagens may also generate these ROS. These ROS may effect in the product of many base of operations adducts, as well as DNA strand breaks and crosslinks.
  • Deaminating agents, for case nitrous acrid which tin crusade transition mutations by converting cytosine to uracil.
  • Polycyclic aromatic hydrocarbons (PAH), when activated to diol-epoxides can bind to Deoxyribonucleic acid and form adducts.
  • Alkylating agents such equally ethylnitrosourea. The compounds transfer methyl or ethyl group to bases or the backbone phosphate groups. Guanine when alkylated may exist mispaired with thymine. Some may cause Deoxyribonucleic acid crosslinking and breakages. Nitrosamines are an important group of mutagens establish in tobacco, and may likewise be formed in smoked meats and fish via the interaction of amines in food with nitrites added every bit preservatives. Other alkylating agents include mustard gas and vinyl chloride.
  • Aromatic amines and amides have been associated with carcinogenesis since 1895 when German physician Ludwig Rehn observed high incidence of bladder cancer amidst workers in German constructed effluvious amine dye manufacture. 2-Acetylaminofluorene, originally used as a pesticide but may also exist found in cooked meat, may cause cancer of the bladder, liver, ear, intestine, thyroid and breast.
  • Alkaloid from plants, such equally those from Vinca species,[35]
    may be converted past metabolic processes into the active mutagen or carcinogen.
  • Bromine and some compounds that comprise bromine in their chemic construction.[36]
  • Sodium azide, an azide salt that is a common reagent in organic synthesis and a component in many car airbag systems
  • Psoralen combined with ultraviolet radiation causes Deoxyribonucleic acid cross-linking and hence chromosome breakage.
  • Benzene, an industrial solvent and precursor in the production of drugs, plastics, constructed rubber and dyes.
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Base analogs

[edit]

  • Base analog, which can substitute for DNA bases during replication and crusade transition mutations.some examples are v bromo uracil and 2 amino purine

Intercalating agents

[edit]

  • Intercalating agents, such as ethidium bromide and proflavine, are molecules that may insert between bases in Dna, causing frameshift mutation during replication. Some such equally daunorubicin may block transcription and replication, making them highly toxic to proliferating cells.[
    citation needed
    ]

Metals

[edit]

Many metals, such equally arsenic, cadmium, chromium, nickel and their compounds may be mutagenic, but they may act, however, via a number of different mechanisms.[37]
Arsenic, chromium, iron, and nickel may be associated with the production of ROS, and some of these may also alter the fidelity of DNA replication. Nickel may likewise be linked to DNA hypermethylation and histone deacetylation, while some metals such as cobalt, arsenic, nickel and cadmium may also touch DNA repair processes such every bit DNA mismatch repair, and base of operations and nucleotide excision repair.[38]

Biological agents

[edit]

  • Transposon, a section of DNA that undergoes autonomous fragment relocation/multiplication. Its insertion into chromosomal DNA disrupts functional elements of the genes.
  • Virus – Virus Deoxyribonucleic acid may be inserted into the genome and disrupts genetic function. Infectious agents accept been suggested to crusade cancer as early on as 1908 by Vilhelm Ellermann and Oluf Bang,[39]
    and 1911 by Peyton Rous who discovered the Rous sarcoma virus.[40]
  • Bacteria – some bacteria such as
    Helicobacter pylori
    cause inflammation during which oxidative species are produced, causing DNA harm and reducing efficiency of DNA repair systems, thereby increasing mutation.

Protection

[edit]

Fruits and vegetables are rich in antioxidants.

Antioxidants are an of import group of anticarcinogenic compounds that may help remove ROS or potentially harmful chemicals. These may be found naturally in fruits and vegetables.[41]
Examples of antioxidants are vitamin A and its carotenoid precursors, vitamin C, vitamin E, polyphenols, and various other compounds. β-Carotene is the red-orangish colored compounds found in vegetables similar carrots and tomatoes. Vitamin C may foreclose some cancers by inhibiting the formation of mutagenic N-nitroso compounds (nitrosamine). Flavonoids, such as EGCG in greenish tea, have also been shown to be effective antioxidants and may have anti-cancer properties. Epidemiological studies indicate that a diet rich in fruits and vegetables is associated with lower incidence of some cancers and longer life expectancy,[42]
withal, the effectiveness of antioxidant supplements in cancer prevention in full general is still the subject of some debate.[42]
[43]

Other chemicals may reduce mutagenesis or prevent cancer via other mechanisms, although for some the precise mechanism for their protective holding may non be certain. Selenium, which is nowadays every bit a micronutrient in vegetables, is a component of of import antioxidant enzymes such equally gluthathione peroxidase. Many phytonutrients may counter the effect of mutagens; for case, sulforaphane in vegetables such every bit broccoli has been shown to be protective against prostate cancer.[44]
Others that may be effective against cancer include indole-3-carbinol from cruciferous vegetables and resveratrol from red wine.[45]

An constructive precautionary measure an individual can undertake to protect themselves is past limiting exposure to mutagens such equally UV radiations and tobacco smoke. In Australia, where people with pale peel are frequently exposed to potent sunlight, melanoma is the most common cancer diagnosed in people aged 15–44 years.[46]
[47]

In 1981, human epidemiological analysis by Richard Doll and Richard Peto indicated that smoking caused 30% of cancers in the US.[48]
Diet is also thought to cause a significant number of cancer, and it has been estimated that around 32% of cancer deaths may be avoidable by modification to the diet.[49]
Mutagens identified in food include mycotoxins from food contaminated with fungal growths, such as aflatoxins which may be present in contaminated peanuts and corn; heterocyclic amines generated in meat when cooked at high temperature; PAHs in charred meat and smoked fish, as well as in oils, fats, bread, and cereal;[50]
and nitrosamines generated from nitrites used as food preservatives in cured meat such as bacon (ascobate, which is added to cured meat, all the same, reduces nitrosamine formation).[41]
Overly-browned starchy food such as bread, biscuits and potatoes tin can generate acrylamide, a chemic shown to crusade cancer in animal studies.[51]
[52]
Excessive booze consumption has also been linked to cancer; the possible mechanisms for its carcinogenicity include germination of the possible mutagen acetaldehyde, and the induction of the cytochrome P450 system which is known to produce mutagenic compounds from promutagens.[53]

For certain mutagens, such every bit unsafe chemicals and radioactive materials, as well as infectious agents known to cause cancer, government legislations and regulatory bodies are necessary for their command.[54]

Test systems

[edit]

Many different systems for detecting mutagen have been adult.[55]
[56]
Animal systems may more than accurately reflect the metabolism of human, notwithstanding, they are expensive and time-consuming (may take around iii years to complete), they are therefore not used as a first screen for mutagenicity or carcinogenicity.

Bacterial

[edit]

  • Ames examination
    – This is the well-nigh usually used test, and
    Salmonella typhimurium
    strains scarce in histidine biosynthesis are used in this test. The test checks for mutants that can revert to wild-blazon. It is an piece of cake, inexpensive and user-friendly initial screen for mutagens.
  • Resistance to eight-azaguanine in
    Southward. typhimurium

    – Similar to Ames examination, but instead of reverse mutation, it checks for forward mutation that confer resistance to 8-Azaguanine in a histidine revertant strain.

  • Escherichia coli
    systems

    – Both forward and reverse mutation detection system take been modified for use in
    E. coli. Tryptophan-deficient mutant is used for the reverse mutation, while galactose utility or resistance to 5-methyltryptophan may be used for frontward mutation.
  • DNA repair

    Due east. coli
    and
    Bacillus subtilis
    strains deficient in DNA repair may exist used to detect mutagens by their effect on the growth of these cells through DNA damage.
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Yeast

[edit]

Systems similar to Ames test have been developed in yeast.
Saccharomyces cerevisiae
is generally used. These systems can check for frontwards and reverse mutations, besides equally recombinant events.


Drosophila


[edit]

Sex-Linked Recessive Lethal Examination
– Males from a strain with yellow bodies are used in this examination. The gene for the yellow body lies on the Ten-chromosome. The fruit flies are fed on a diet of test chemical, and progenies are separated by sexual practice. The surviving males are crossed with the females of the same generation, and if no males with yellow bodies are detected in the 2d generation, it would indicate a lethal mutation on the Ten-chromosome has occurred.

Plant assays

[edit]

Plants such as
Zea mays,
Arabidopsis thaliana
and
Tradescantia
have been used in various exam assays for mutagenecity of chemicals.

Cell culture assay

[edit]

Mammalian cell lines such equally Chinese hamster V79 cells, Chinese hamster ovary (CHO) cells or mouse lymphoma cells may be used to test for mutagenesis. Such systems include the
HPRT assay
for resistance to 8-azaguanine or half dozen-thioguanine, and
ouabain-resistance (OUA) assay.

Rat primary hepatocytes may also exist used to mensurate Deoxyribonucleic acid repair following Deoxyribonucleic acid impairment. Mutagens may stimulate unscheduled Deoxyribonucleic acid synthesis that results in more stained nuclear cloth in cells following exposure to mutagens.

Chromosome check systems

[edit]

These systems check for large scale changes to the chromosomes and may exist used with cell civilization or in animal test. The chromosomes are stained and observed for whatsoever changes.
Sister chromatid exchange
is a symmetrical commutation of chromosome material between sister chromatids and may be correlated to the mutagenic or carcinogenic potential of a chemical. In
micronucleus Exam, cells are examined for micronuclei, which are fragments or chromosomes left behind at anaphase, and is therefore a exam for clastogenic agents that cause chromosome breakages. Other tests may check for various chromosomal aberrations such equally chromatid and chromosomal gaps and deletions, translocations, and ploidy.

Beast examination systems

[edit]

Rodents are normally used in brute test. The chemicals under test are commonly administered in the nutrient and in the drinking water, merely sometimes by dermal application, by gavage, or past inhalation, and carried out over the major part of the life span for rodents. In tests that check for carcinogens, maximum tolerated dosage is kickoff determined, so a range of doses are given to around l animals throughout the notional lifespan of the animal of two years. Afterward death the animals are examined for sign of tumours. Differences in metabolism between rat and human yet means that human may not respond in exactly the aforementioned way to mutagen, and dosages that produce tumours on the animate being exam may also exist unreasonably high for a human being, i.e. the equivalent amount required to produce tumours in human may far exceed what a person might run into in existent life.

Mice with recessive mutations for a visible phenotype may too be used to bank check for mutagens. Females with recessive mutation crossed with wild-type males would yield the same phenotype as the wild-type, and any observable change to the phenotype would signal that a mutation induced by the mutagen has occurred.

Mice may also be used for
dominant lethal assays
where early embryonic deaths are monitored. Male mice are treated with chemicals under test, mated with females, and the females are then sacrificed before parturition and early fetal deaths are counted in the uterine horns.

Transgenic mouse assay
using a mouse strain infected with a viral shuttle vector is another method for testing mutagens. Animals are first treated with suspected mutagen, the mouse Dna is then isolated and the phage segment recovered and used to infect
E. coli. Using similar method as the blue-white screen, the plaque formed with Deoxyribonucleic acid containing mutation are white, while those without are blue.

In anti-cancer therapy

[edit]

Many mutagens are highly toxic to proliferating cells, and they are ofttimes used to destroy cancer cells. Alkylating agents such as cyclophosphamide and cisplatin, likewise as intercalating amanuensis such as daunorubicin and doxorubicin may be used in chemotherapy. However, due to their effect on other cells which are likewise rapidly dividing, they may have side furnishings such equally pilus loss and nausea. Research on better targeted therapies may reduce such side-effects. Ionizing radiation are used in radiation therapy.

In fiction

[edit]

In science fiction, mutagens are often represented every bit substances that are capable of completely changing the grade of the recipient or granting them superpowers. Powerful radiations are the agents of mutation for the superheroes in Curiosity Comics’s Fantastic 4, Daredevil, and Hulk, while in the Teenage Mutant Ninja Turtles franchise the mutagen is a chemical agent also called “ooze”, and for Inhumans the mutagen is the Terrigen Mist. Mutagens are likewise featured in video games such as
Cyberia,
The Witcher,
Metroid Prime: Trilogy,
Resistance: Fall of Homo,
Resident Evil,
Infamous,
Freedom Force, Command & Conquer,
Gears of War three,
StarCraft,
BioShock,
Fallout,
Underrail, and
Maneater. In the “nuclear monster” films of the 1950s, nuclear radiations mutates humans and common insects frequently to enormous size and aggression; these films include
Godzilla,
Them!,
Attack of the 50 Foot Woman,
Tarantula!, and
The Amazing Colossal Human being.

Encounter also

[edit]

  • Carcinogenesis
  • DNA damage (naturally occurring)
  • Linear no-threshold model

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[edit]


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Popular:   Which of the Following is Not True of Saliva

Which is Considered a Chemical Mutagen

Source: https://en.wikipedia.org/wiki/Mutagen