Contents 1 Radiation 2 In prepared food 3 In cigarettes 4 Mechanisms of carcinogenicity 5 Classification 5.1 International Agency for Research on Cancer 5.2 Globally Harmonized System 5.3 U.S. National Toxicology Program 5.4 American Conference of Governmental Industrial Hygienists 5.5 European Union 5.6 Safe Work Australia 6 Procarcinogen 7 Common carcinogens 7.1 Occupational carcinogens 7.2 Others 8 Major carcinogens implicated in the four most common cancers worldwide 8.1 Lung cancer 8.2 Breast cancer 8.3 Colon cancer 8.4 Stomach cancer 9 See also 10 References 11 External links


Radiation[edit] Main article: radiation-induced cancer CERCLA identifies all radionuclides as carcinogens, although the nature of the emitted radiation (alpha, beta, gamma, or neutron and the radioactive strength), its consequent capacity to cause ionization in tissues, and the magnitude of radiation exposure, determine the potential hazard. Carcinogenicity of radiation depends on the type of radiation, type of exposure, and penetration. For example, alpha radiation has low penetration and is not a hazard outside the body, but emitters are carcinogenic when inhaled or ingested. For example, Thorotrast, a (incidentally radioactive) suspension previously used as a contrast medium in x-ray diagnostics, is a potent human carcinogen known because of its retention within various organs and persistent emission of alpha particles. Low-level ionizing radiation may induce irreparable DNA damage (leading to replicational and transcriptional errors needed for neoplasia or may trigger viral interactions) leading to pre-mature aging and cancer.[8][9][10] Not all types of electromagnetic radiation are carcinogenic. Low-energy waves on the electromagnetic spectrum including radio waves, microwaves, infrared radiation and visible light are thought not to be, because they have insufficient energy to break chemical bonds. Evidence for carcinogenic effects of non-ionizing radiation is generally inconclusive, though there are some documented cases of radar technicians with prolonged high exposure experiencing significantly higher cancer incidence.[11] Higher-energy radiation, including ultraviolet radiation (present in sunlight), x-rays, and gamma radiation, generally is carcinogenic, if received in sufficient doses. For most people, ultraviolet radiations from sunlight is the most common cause of skin cancer. In Australia, where people with pale skin are often exposed to strong sunlight, melanoma is the most common cancer diagnosed in people aged 15–44 years.[12][13] Substances or foods irradiated with electrons or electromagnetic radiation (such as microwave, X-ray or gamma) are not carcinogenic.[citation needed] In contrast, non-electromagnetic neutron radiation produced inside nuclear reactors can produce secondary radiation through nuclear transmutation.


In prepared food[edit] See also: Cooking § Carcinogens, and Raw foodism Chemicals used in processed and cured meat such as some brands of bacon, sausages and ham may or may not produce carcinogens.[14] For example, nitrites used as food preservatives in cured meat such as bacon have also been noted as being carcinogenic with demographic links, but not causation, to colon cancer.[15] Cooking food at high temperatures, for example grilling or barbecuing meats, can, or can not, also lead to the formation of minute quantities of many potent carcinogens that are comparable to those found in cigarette smoke (i.e., benzo[a]pyrene).[16] Charring of food looks like coking and tobacco pyrolysis, and produces carcinogens. There are several carcinogenic pyrolysis products, such as polynuclear aromatic hydrocarbons, which are converted by human enzymes into epoxides, which attach permanently to DNA. Pre-cooking meats in a microwave oven for 2–3 minutes before grilling shortens the time on the hot pan, and removes heterocyclic amine (HCA) precursors, which can help minimize the formation of these carcinogens.[17] Reports from the Food Standards Agency have found that the known animal carcinogen acrylamide is generated in fried or overheated carbohydrate foods (such as french fries and potato chips).[18] Studies are underway at the FDA and European regulatory agencies to assess its potential risk to humans.


In cigarettes[edit] Main article: Tobacco and health There is a strong association of smoking with lung cancer; the lifetime risk of developing lung cancer increases significantly in smokers.[19] A large number of known carcinogens are found in cigarette smoke. Potent carcinogens found in cigarette smoke include polycyclic aromatic hydrocarbons (PAH, such as benzo[a]pyrene), Benzene, and Nitrosamine.[20]


Mechanisms of carcinogenicity[edit] Carcinogens can be classified as genotoxic or nongenotoxic. Genotoxins cause irreversible genetic damage or mutations by binding to DNA. Genotoxins include chemical agents like N-nitroso-N-methylurea (NMU) or non-chemical agents such as ultraviolet light and ionizing radiation. Certain viruses can also act as carcinogens by interacting with DNA. Nongenotoxins do not directly affect DNA but act in other ways to promote growth. These include hormones and some organic compounds.[21]


Classification[edit] Approximate equivalences between classification schemes IARC GHS NTP ACGIH EU Group 1 Cat. 1A Known A1 Cat. 1 Group 2A Cat. 1B Reasonably suspected A2 Cat. 2 Group 2B Cat. 2   A3 Cat. 3 Group 3   A4   Group 4 A5 International Agency for Research on Cancer[edit] The International Agency for Research on Cancer (IARC) is an intergovernmental agency established in 1965, which forms part of the World Health Organization of the United Nations. It is based in Lyon, France. Since 1971 it has published a series of Monographs on the Evaluation of Carcinogenic Risks to Humans[22] that have been highly influential in the classification of possible carcinogens. Group 1: the agent (mixture) is definitely carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans. Group 2A: the agent (mixture) is probably carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans. Group 2B: the agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans. Group 3: the agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. Group 4: the agent (mixture) is probably not carcinogenic to humans. Globally Harmonized System[edit] The Globally Harmonized System of Classification and Labelling of Chemicals (GHS) is a United Nations initiative to attempt to harmonize the different systems of assessing chemical risk which currently exist (as of March 2009) around the world. It classifies carcinogens into two categories, of which the first may be divided again into subcategories if so desired by the competent regulatory authority: Category 1: known or presumed to have carcinogenic potential for humans Category 1A: the assessment is based primarily on human evidence Category 1B: the assessment is based primarily on animal evidence Category 2: suspected human carcinogens U.S. National Toxicology Program[edit] The National Toxicology Program of the U.S. Department of Health and Human Services is mandated to produce a biennial Report on Carcinogens.[23] As of June 2011, the latest edition was the 12th report (2011).[6] It classifies carcinogens into two groups: Known to be a human carcinogen Reasonably anticipated being a human carcinogen American Conference of Governmental Industrial Hygienists[edit] The American Conference of Governmental Industrial Hygienists (ACGIH) is a private organization best known for its publication of threshold limit values (TLVs) for occupational exposure and monographs on workplace chemical hazards. It assesses carcinogenicity as part of a wider assessment of the occupational hazards of chemicals. Group A1: Confirmed human carcinogen Group A2: Suspected human carcinogen Group A3: Confirmed animal carcinogen with unknown relevance to humans Group A4: Not classifiable as a human carcinogen Group A5: Not suspected as a human carcinogen European Union[edit] The European Union classification of carcinogens is contained in the Dangerous Substances Directive and the Dangerous Preparations Directive. It consists of three categories: Category 1: Substances known to be carcinogenic to humans. Category 2: Substances which should be regarded as if they are carcinogenic to humans. Category 3: Substances which cause concern for humans, owing to possible carcinogenic effects but in respect of which the available information is not adequate for making a satisfactory assessment. This assessment scheme is being phased out in favor of the GHS scheme (see above), to which it is very close in category definitions. Safe Work Australia[edit] Under a previous name, the NOHSC, in 1999 Safe Work Australia published the Approved Criteria for Classifying Hazardous Substances [NOHSC:1008(1999)].[24] Section 4.76 of this document outlines the criteria for classifying carcinogens as approved by the Australian government. This classification consists of three categories: Category 1: Substances known to be carcinogenic to humans. Category 2: Substances that should be regarded as if they were carcinogenic to humans. Category 3: Substances that have possible carcinogenic effects in humans but about which there is insufficient information to make an assessment.


Procarcinogen[edit] A procarcinogen is a precursor to a carcinogen. One example is nitrites when taken in by the diet. They are not carcinogenic themselves, but turn into nitrosamines in the body, which can be carcinogenic.[25]


Common carcinogens[edit] Occupational carcinogens[edit] Occupational carcinogens are agents that pose a risk of cancer in several specific work-locations: Carcinogen Associated cancer sites or types Occupational uses or sources Arsenic and its compounds Lung Skin Hemangiosarcoma Smelting byproduct Component of: Alloys Electrical and semiconductor devices Medications (e.g. melarsoprol) Herbicides Fungicides Animal dips Drinking water from contaminated aquifers. Asbestos Lungs Asbestosis Gastrointestinal tract Pleural Mesothelioma Peritoneal Mesothelioma Not in widespread use, but found in: Constructions Roofing papers Floor tiles Fire-resistant textiles Friction linings (brake pads) (only outside Europe) Replacement friction linings for automobiles still may contain asbestos Benzene Leukemia Hodgkin's lymphoma Light fuel oil Former use as solvent and fumigant Printing Lithography Paint Rubber Dry cleaning Adhesives Coatings Detergents Beryllium and its compounds Lung Missile fuel Lightweight alloys Aerospace applications Nuclear reactors Cadmium and its compounds[26] Prostate Yellow pigments Phosphors Solders Batteries Metal paintings and coatings Hexavalent chromium(VI) compounds Lung Paints Pigments Preservatives IC engine exhaust gas Lung[27] Bladder[27] Exhaust gas from engines Ethylene oxide Leukemia Ripening agent for fruits and nuts Rocket propellant Fumigant for foodstuffs and textiles Sterilant for hospital equipment Nickel Nose Lung Nickel plating Ferrous alloys Ceramics Batteries Stainless-steel welding byproduct Radon and its decay products Lung Uranium decay Quarries and mines Cellars and poorly ventilated places Vinyl chloride Hemangiosarcoma Liver Refrigerant Production of polyvinyl chloride Adhesive for plastics Former use in pressurized containers Shift work that involves circadian disruption[28] Breast Involuntary smoking (Passive smoking)[29] Lung Radium-226, Radium-224, Plutonium-238, Plutonium-239[30] and other alpha particle emitters with high atomic weight Bone (they are bone seekers) Liver Nuclear fuel processing Radium dial manufacturing Unless otherwise specified, ref is:[31] Others[edit] Gasoline (contains aromatics) Lead and its compounds Alkylating antineoplastic agents (e.g. mechlorethamine) Other alkylating agents (e.g. dimethyl sulfate) Ultraviolet radiation from the sun and UV lamps Alcohol (causing head and neck cancers) Other ionizing radiation (X-rays, gamma rays, etc.)


Major carcinogens implicated in the four most common cancers worldwide[edit] In this section, the carcinogens implicated as the main causative agents of the four most common cancers worldwide are briefly described. These four cancers are lung, breast, colon, and stomach cancers. Together they account for about 41% of worldwide cancer incidence and 42% of cancer deaths (for more detailed information on the carcinogens implicated in these and other cancers, see references[32][33]). Lung cancer[edit] Lung cancer (pulmonary carcinoma) is the most common cancer in the world, both in terms of cases (1.6 million cases; 12.7% of total cancer cases) and deaths (1.4 million deaths; 18.2% of total cancer deaths).[34] Lung cancer is largely caused by tobacco smoke. Risk estimates for lung cancer in the United States indicate that tobacco smoke is responsible for 90% of lung cancers. Other factors are implicated in lung cancer, and these factors can interact synergistically with smoking so that total attributable risk adds up to more than 100%. These factors include occupational exposure to carcinogens (about 9-15%), radon (10%) and outdoor air pollution (1-2%).[35] Tobacco smoke is a complex mixture of more than 5,300 identified chemicals. The most important carcinogens in tobacco smoke have been determined by a “Margin of Exposure” approach.[36] Using this approach, the most important tumorigenic compounds in tobacco smoke were, in order of importance, acrolein, formaldehyde, acrylonitrile, 1,3-butadiene, cadmium, acetaldehyde, ethylene oxide, and isoprene. Most of these compounds cause DNA damage by forming DNA adducts or by inducing other alterations in DNA.[33] DNA damages are subject to error-prone DNA repair or can cause replication errors. Such errors in repair or replication can result in mutations in tumor suppressor genes or oncogenes leading to cancer. Breast cancer[edit] Breast cancer is the second most common cancer [(1.4 million cases, 10.9%), but ranks 5th as cause of death (458,000, 6.1%)].[34] Increased risk of breast cancer is associated with persistently elevated blood levels of estrogen.[37] Estrogen appears to contribute to breast carcinogenesis by three processes; (1) the metabolism of estrogen to genotoxic, mutagenic carcinogens, (2) the stimulation of tissue growth, and (3) the repression of phase II detoxification enzymes that metabolize ROS leading to increased oxidative DNA damage.[38][39][40] The major estrogen in humans, estradiol, can be metabolized to quinone derivatives that form adducts with DNA.[41] These derivatives can cause dupurination, the removal of bases from the phosphodiester backbone of DNA, followed by inaccurate repair or replication of the apurinic site leading to mutation and eventually cancer. This genotoxic mechanism may interact in synergy with estrogen receptor-mediated, persistent cell proliferation to ultimately cause breast cancer.[41] Genetic background, dietary practices and environmental factors also likely contribute to the incidence of DNA damage and breast cancer risk. Colon cancer[edit] Colorectal cancer is the third most common cancer [1.2 million cases (9.4%), 608,000 deaths (8.0%)].[34] Tobacco smoke may be responsible for up to 20% of colorectal cancers in the United States.[42] In addition, substantial evidence implicates bile acids as an important factor in colon cancer. Twelve studies (summarized in Bernstein et al.[43]) indicate that the bile acids deoxycholic acid (DCA) and/or lithocholic acid (LCA) induce production of DNA-damaging reactive oxygen species and/or reactive nitrogen species in human or animal colon cells. Furthermore, 14 studies showed that DCA and LCA induce DNA damage in colon cells. Also 27 studies reported that bile acids cause programmed cell death (apoptosis). Increased apoptosis can result in selective survival of cells that are resistant to induction of apoptosis.[43] Colon cells with reduced ability to undergo apoptosis in response to DNA damage would tend to accumulate mutations, and such cells may give rise to colon cancer.[43] Epidemiologic studies have found that fecal bile acid concentrations are increased in populations with a high incidence of colon cancer. Dietary increases in total fat or saturated fat result in elevated DCA and LCA in feces and elevated exposure of the colon epithelium to these bile acids. When the bile acid DCA was added to the standard diet of wild-type mice invasive colon cancer was induced in 56% of the mice after 8 to 10 months.[44] Overall, the available evidence indicates that DCA and LCA are centrally important DNA-damaging carcinogens in colon cancer. Stomach cancer[edit] Stomach cancer is the fourth most common cancer [990,000 cases (7.8%), 738,000 deaths (9.7%)].[34] Helicobacter pylori infection is the main causative factor in stomach cancer. Chronic gastritis (inflammation) caused by H. pylori is often long-standing if not treated. Infection of gastric epithelial cells with H. pylori results in increased production of reactive oxygen species (ROS).[45][46] ROS cause oxidative DNA damage including the major base alteration 8-hydroxydeoxyguanosine (8-OHdG). 8-OHdG resulting from ROS is increased in chronic gastritis. The altered DNA base can cause errors during DNA replication that have mutagenic and carcinogenic potential. Thus H. pylori-induced ROS appear to be the major carcinogens in stomach cancer because they cause oxidative DNA damage leading to carcinogenic mutations. Diet is thought to be a contributing factor in stomach cancer - in Japan where very salty pickled foods are popular, the incidence of stomach cancer is high. Preserved meat such as bacon, sausages, and ham increases the risk while a diet high in fresh fruit and vegetables may reduce the risk. The risk also increases with age.[47]


See also[edit] Acrylamide Asian Dust History of cancer Industrial Union Department v. American Petroleum Institute International Agency for Research on Cancer Mutagen Possible carcinogen Safe handling of carcinogens Teratogen Warburg hypothesis


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External links[edit] Look up carcinogen in Wiktionary, the free dictionary. Wikimedia Commons has media related to Carcinogens. U.S. National Toxicology Program's Report on Carcinogens CDC – Occupational Cancer – Carcinogen List – NIOSH Safety and Health Topic Recognized Carcinogens American Cancer Society Database of Rodent Carcinogens Comparing Possible Cancer Hazards from Human Exposures to Rodent Carcinogens v t e Cancer-causing materials and agents (carcinogens) Cancer Cancer cells Prominent human carcinogens Acetaldehyde Arsenic Asbestos Bacteria Helicobacter Pylori Benzo[a]pyrene Bisphenol A 1,3-Butadiene Diethylstilbestrol Formaldehyde Ionizing radiation (e.g., from isotopes of plutonium and radium) Tobacco smoke Ultraviolet light Viruses Epstein–Barr Hepatitis B Hepatitis C Human papillomavirus IARC lists Group 1 Group 2A Group 2B Group 3 Caprolactam (Group 4) #WHO-EM ‡Withdrawn from market Clinical trials: †Phase III §Never to phase III v t e Overview of tumors, cancer and oncology (C00–D48, 140–239) Conditions Benign tumors Hyperplasia Cyst Pseudocyst Hamartoma Malignant progression Dysplasia Carcinoma in situ Cancer Metastasis Primary tumor Sentinel lymph node Topography Head/Neck (Oral, Nasopharyngeal) Digestive system Respiratory system Bone Skin Blood Urogenital Nervous system Endocrine system Histology Carcinoma Sarcoma Blastoma Papilloma Adenoma Other Precancerous condition Paraneoplastic syndrome Staging/grading TNM Ann Arbor Prostate cancer staging Gleason grading system Dukes classification Carcinogenesis Cancer cell Carcinogen Tumor suppressor genes/oncogenes Clonally transmissible cancer Oncovirus Carcinogenic bacteria Misc. Research Index of oncology articles History Cancer pain Cancer and nausea v t e Toxicology History of poison Toxinology Fields Aquatic toxicology Ecotoxicology Occupational toxicology Entomotoxicology Environmental toxicology Forensic toxicology Medical toxicology In vitro toxicology Toxicogenomics Concepts Acceptable daily intake Acute toxicity Bioaccumulation Biomagnification Fixed Dose Procedure Lethal dose Poison Toxic capacity Toxicant Toxin Toxicity Class Venom Treatments Activated carbon Antidote Cathartic Chelation therapy Gastric lavage Hemodialysis Hemoperfusion Whole bowel irrigation Incidents 1858 Bradford sweets poisoning 2007 pet food recalls Bhopal disaster Minamata disease Niigata Minamata disease Poisoning of Alexander Litvinenko Seveso disaster Consumption of Tide Pods List of poisonings Related topics Biological warfare Carcinogen Food safety Hazard symbol List of extremely hazardous substances Mutagen Occupational safety and health Category Commons WikiProject v t e Genotoxicity Agent Mutagen Clastogen Aneugen Carcinogen Assays Ames test Comet assay algal test Seed testing Viability test (TZ test) Microtox bioassay Category Commons WikiProject v t e Health issues of plastics and polyhalogenated compounds (PHCs) Plasticizers: Phthalates DIBP DBP BBP (BBzP) DIHP DEHP (DOP) DIDP DINP Miscellaneous plasticizers Organophosphates Adipates (DEHA DOA) Monomers Bisphenol A (BPA, in Polycarbonates) Vinyl chloride (in PVC) Miscellaneous additives incl. PHCs PBDEs PCBs Organotins PFCs Perfluorooctanoic acid Health issues Teratogen Carcinogen Endocrine disruptor Diabetes Obesity Obesogen Polymer fume fever Pollution Plastic pollution Great Pacific garbage patch Persistent organic pollutant Dioxins List of environmental health hazards Regulations California Proposition 65 European REACH regulation Japan Toxic Substances Law Toxic Substances Control Act Retrieved from "https://en.wikipedia.org/w/index.php?title=Carcinogen&oldid=826856368" Categories: CarcinogensCarcinogenesisRadiation health effectsHidden categories: Webarchive template wayback linksArticles with inconsistent citation formatsAll articles with unsourced statementsArticles with unsourced statements from July 2010Pages using div col without cols and colwidth parametersPages using Columns-list with deprecated parameters


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