Editing Mutagen (section)

==Types of Mutagens==
Mutagens may be of physical, chemical or biological origin. They may act directly on the DNA, causing direct damage to the DNA, and most often result in replication error. Some however may act on the replication mechanism and chromosomal partition. Many mutagens are not mutagenic by themselves, but can form mutagenic metabolites through cellular processes, for example through the activity of the [[cytochrome P450]] system and other [[oxygenase]]s such as [[cyclooxygenase]].<ref>{{cite journal | vauthors = Kim D, Guengerich FP | title = Cytochrome P450 activation of arylamines and heterocyclic amines | journal = Annual Review of Pharmacology and Toxicology | volume = 45 | pages = 27–49 | date = 2005 | pmid = 15822170 | doi = 10.1146/annurev.pharmtox.45.120403.100010 }}</ref> Such mutagens are called [[promutagens]].{{fact|date=January 2025}}

===Physical mutagens===
* [[Ionizing radiation]]s such as [[X-rays]], [[gamma ray]]s and [[alpha particle]]s cause DNA breakage and other damages. The most common lab sources include [[cobalt-60]] and [[cesium-137]].
* [[Ultraviolet]] radiations with wavelength above 260&nbsp;nm are absorbed strongly by bases, producing [[pyrimidine dimers]], which can cause error in replication if left uncorrected.
* [[Radioactive decay]], such as [[Carbon-14|<sup>14</sup>C]] in DNA which decays into [[nitrogen]].

===Chemical mutagens===
[[Image:Benzopyrene DNA adduct 1JDG.png|thumb |right |200px |A [[DNA adduct]] (at center) of the mutagenic [[(+)-Benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide|metabolite]] of [[Benzo(a)pyrene|benzo[''a'']pyrene]] from [[tobacco smoking|tobacco smoke]]]]
Chemical mutagens either directly or indirectly damage DNA. On this basis, they are of 2 types:

====Directly acting chemical mutagens====
They directly damage DNA, but may or may not undergo metabolism to produce promutagens (metabolites that can have higher mutagenic potential than their substrates).
* [[Reactive oxygen species]] (ROS) – These may be [[superoxide]], [[hydroxyl radicals]] and [[hydrogen peroxide]], and large number of these highly reactive species are generated by normal cellular processes, for example as a by-products of mitochondrial [[Electron transport chain|electron transport]], or [[lipid peroxidation]]. As an example of the latter, 15-hydroperoxyeicosatetraenoic acid, a natural product of cellular cyclooxygenases and lipoxygenases, breaks down to form 4-hydroxy-2(''E'')-nonenal, 4-hydroperoxy-2(''E'')-nonenal, 4-oxo-2(''E'')-nonenal, and ''cis''-4,5-epoxy-2(''E'')-decanal; these bifunctional electophils are mutagenic in mammalian cells and may contribute to the development and/or progression of human cancers (see [[15-Hydroxyicosatetraenoic acid]]).<ref>{{cite journal | vauthors = Lee SH, Williams MV, Dubois RN, Blair IA | title = Cyclooxygenase-2-mediated DNA damage | journal = The Journal of Biological Chemistry | volume = 280 | issue = 31 | pages = 28337–46 | date = August 2005 | pmid = 15964853 | doi = 10.1074/jbc.M504178200 | display-authors = 3 | doi-access = free }}</ref> A number of mutagens may also generate these ROS. These ROS may result in the production of many base adducts, as well as DNA strand breaks and crosslinks.
* [[Deamination|Deaminating]] agents, for example [[nitrous acid]] which can cause transition mutations by converting [[cytosine]] to [[uracil]].
* [[Polycyclic aromatic hydrocarbon]]s (PAH), when activated to diol-epoxides can bind to DNA and form adducts.
* [[Alkylation|Alkylating]] agents such as [[ethylnitrosourea]]. The compounds transfer methyl or ethyl group to bases or the backbone phosphate groups. Guanine when alkylated may be mispaired with thymine. Some may cause DNA crosslinking and breakages. [[Nitrosamine]]s are an important group of mutagens found in tobacco, and may also be formed in smoked meats and fish via the interaction of amines in food with nitrites added as preservatives. Other alkylating agents include [[Sulfur mustard|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 among workers in German synthetic aromatic amine dye industry. [[2-Acetylaminofluorene]], originally used as a pesticide but may also be found in cooked meat, may cause cancer of the bladder, liver, ear, intestine, thyroid and breast.
* [[Alkaloid]] from plants, such as those from [[Vinca]] species,<ref>{{cite book |doi=10.1016/S0378-6080(05)80467-2 |chapter=Cytostatic drugs |title=Side Effects of Drugs Annual 28 |date=2005 |last1=Lipp |first1=Hans-Peter |last2=Hartmann |first2=Jörg Thomas |last3=Stanley |first3=Andrew |volume=28 |pages=538–551 |isbn=978-0-444-51571-1 }}</ref> may be converted by metabolic processes into the active mutagen or carcinogen.
* [[Bromine]] and some compounds that contain bromine in their chemical structure.<ref>{{cite journal | vauthors = Henderson JP, Byun J, Williams MV, Mueller DM, McCormick ML, Heinecke JW | title = Production of brominating intermediates by myeloperoxidase. A transhalogenation pathway for generating mutagenic nucleobases during inflammation | journal = The Journal of Biological Chemistry | volume = 276 | issue = 11 | pages = 7867–75 | date = March 2001 | pmid = 11096071 | doi = 10.1074/jbc.M005379200 | display-authors = 3 | doi-access = free }}</ref>
* [[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 DNA cross-linking and hence chromosome breakage.
* [[Benzene]], an industrial solvent and precursor in the production of drugs, plastics, [[synthetic rubber]] and dyes.
* [[Chromium trioxide]], a highly toxic and oxidizing substance used in electroplating.<ref>{{cite journal | last1=Mamyrbaev | first1=Arstan Abdramanovich | last2=Dzharkenov | first2=Timur Agataevich | last3=Imangazina | first3=Zina Amangalievna | last4=Satybaldieva | first4=Umit Abulkhairovna | title=Mutagenic and carcinogenic actions of chromium and its compounds | journal=Environmental Health and Preventive Medicine | publisher=Springer Science and Business Media LLC | volume=20 | issue=3 | date=2015-04-16 | issn=1342-078X | doi=10.1007/s12199-015-0458-2 | pages=159–167| pmid=25877777 | pmc=4434237| bibcode=2015EHPM...20..159M }}</ref>

====Indirectly acting chemical mutagens====
They are not necessarily mutagenic by themselves, but they produce promutagens mutagenic compounds through metabolic processes in cells.
*[[Polyaromatic hydrocarbon]]s (PAHs)<ref>{{Cite journal |last=Yu |first=Hongtao |date=November 2002 |title=Environmental carcinogenic polycyclic aromatic hydrocarbons: photochemistry and phototoxicity |journal=Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews |volume=20 |issue=2 |pages=149–183 |doi=10.1081/GNC-120016203 |issn=1059-0501 |pmc=3812823 |pmid=12515673|bibcode=2002JESHC..20..149Y }}</ref>
*[[Aromatic amine]]s<ref>{{Cite book |last1=Cooke |first1=M. |last2=Dennis |first2=A. J. |date=1986-01-01 |title=Polynuclear aromatic hydrocarbons: Chemistry, characterization and carcinogenesis |osti=7252502 |url=https://www.osti.gov/biblio/7252502}}</ref>
*[[Benzene]]<ref>{{Cite journal |last1=Nishikawa |first1=Takuro |last2=Miyahara |first2=Emiko |last3=Horiuchi |first3=Masahisa |last4=Izumo |first4=Kimiko |last5=Okamoto |first5=Yasuhiro |last6=Kawai |first6=Yoshichika |last7=Kawano |first7=Yoshifumi |last8=Takeuchi |first8=Toru |date=January 2012 |title=Benzene metabolite 1,2,4-benzenetriol induces halogenated DNA and tyrosines representing halogenative stress in the HL-60 human myeloid cell line |journal=Environmental Health Perspectives |volume=120 |issue=1 |pages=62–67 |doi=10.1289/ehp.1103437 |issn=1552-9924 |pmc=3261936 |pmid=21859636|bibcode=2012EnvHP.120...62N }}</ref>

Some chemical mutagens additionally require [[UV light|UV]] or [[visible light]] activation for their mutagenic effect.  These are the {{vanchor|photomutagens|Photomutagen}}, which include [[furocoumarin]]s and [[limettin]].<ref>{{cite journal|last1=Raquet|first1=N|last2=Schrenk|first2=D|title=Relative photomutagenicity of furocoumarins and limettin in the hypoxanthine phosphoribosyl transferase assay in V79 cells.|journal=Chemical Research in Toxicology|date=September 2009|volume=22|issue=9|pages=1639–47|pmid=19725558|doi=10.1021/tx9002287}}</ref>

===Base analogs===
* [[Base analog]], which can substitute for DNA bases during replication and cause transition mutations. Some examples are [[5-Bromouracil|5-bromouracil]] and [[2-Aminopurine|2-aminopurine]].

===Intercalating agents===
* [[Intercalation (biochemistry)|Intercalating agents]], such as [[ethidium bromide]] and [[proflavine]], are molecules that may insert between bases in DNA, causing [[frameshift mutation]] during replication. Some such as [[daunorubicin]] may block transcription and replication, making them highly toxic to proliferating cells.{{citation needed|date=July 2022}}

===Metals===
Many metals, such as [[arsenic]], [[cadmium]], [[chromium]], [[nickel]] and their compounds may be mutagenic, but they may act, however, via a number of different mechanisms.<ref>{{cite journal |last1=Valko |first1=M. |last2=Morris |first2=H. |last3=Cronin |first3=M. |title=Metals, Toxicity and Oxidative Stress |journal=Current Medicinal Chemistry |date=May 2005 |volume=12 |issue=10 |pages=1161–1208 |doi=10.2174/0929867053764635 |pmid=15892631 }}</ref> 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 also be linked to DNA hypermethylation and [[histone]] deacetylation, while some metals such as [[cobalt]], arsenic, nickel and cadmium may also affect DNA repair processes such as [[DNA mismatch repair]], and [[Base excision repair|base]] and [[nucleotide excision repair]].<ref>{{cite web|url=http://www.ebrc.de/industrial-chemicals-reach/projects-and-references/downloads/HERAG_FS_05_August_07.pdf|title=Health Risk Assessment Guidance for Metals – Mutagenicity|date=2007|work=EBRC|archive-url=https://web.archive.org/web/20120412230532/http://www.ebrc.de/industrial-chemicals-reach/projects-and-references/downloads/HERAG_FS_05_August_07.pdf|archive-date=12 April 2012}}</ref>

===Biological agents===
* [[Transposon]]s, a section of DNA that undergoes autonomous fragment relocation/multiplication. Its insertion into chromosomal DNA disrupts functional elements of the genes.
* [[Oncovirus]]es – Virus DNA may be inserted into the genome and disrupts genetic function. Infectious agents have been suggested to cause cancer as early as 1908 by Vilhelm Ellermann and Oluf Bang,<ref>{{cite journal |author1=Ellermann V. |author2=Bang O. |title=Experimentelle Leukämie bei Hühnern |journal=Zentralbl. Bakteriol. Parasitenkd. Infectionskr. Hyg. Abt. Orig. |year=1908 |volume=46 |pages=595–609 }}</ref> and 1911 by [[Peyton Rous]] who discovered the [[Rous sarcoma virus]].<ref>{{cite journal | vauthors = Rous P | journal = The Journal of Experimental Medicine | volume = 13 | issue = 4 | pages = 397–411 | date = April 1911 | pmid = 19867421 | pmc = 2124874 | doi = 10.1084/jem.13.4.397 | title = A Sarcoma of the Fowl Transmissible by an Agent Separable from the Tumor Cells }}</ref>
* [[Bacteria]] – some bacteria such as ''[[Helicobacter pylori]]'' cause inflammation during which oxidative species are produced, causing DNA damage and reducing efficiency of DNA repair systems, thereby increasing mutation.