A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substances are considered carcinogens, but their carcinogenic activity is attributed to the radiation, for example gamma rays and alpha particles, which they emit. Common examples of non-radioactive carcinogens are inhaled asbestos, certain dioxins, and tobacco smoke. Although the public generally associates carcinogenicity with synthetic chemicals, it is equally likely to arise in both natural and synthetic substances.
Cancer is any disease in which normal cells are damaged and do not undergo programmed cell death as fast as they divide via mitosis. Carcinogens may increase the risk of cancer by altering cellular metabolism or damaging DNA directly in cells, which interferes with biological processes, and induces the uncontrolled, malignant division, ultimately leading to the formation of tumors. Usually, severe DNA damage leads to apoptosis, but if the programmed cell death pathway is damaged, then the cell cannot prevent itself from becoming a cancer cell.
There are many natural carcinogens. Aflatoxin B1, which is produced by the fungus Aspergillus flavus growing on stored grains, nuts and peanut butter, is an example of a potent, naturally occurring microbial carcinogen. Certain viruses such as Hepatitis B and human papilloma virus have been found to cause cancer in humans. The first one shown to cause cancer in animals is Rous sarcoma virus, discovered in 1910 by Peyton Rous.
Dioxins and dioxin-like compounds, benzene, kepone, EDB, and asbestos have all been classified as carcinogenic. As far back as the 1930s, industrial smoke and tobacco smoke were identified as sources of dozens of carcinogens, including benzo[a]pyrene, tobacco-specific nitrosamines such as nitrosonornicotine, and reactive aldehydes such as formaldehyde—which is also a hazard in embalming and making plastics. Vinyl chloride, from which PVC is manufactured, is a carcinogen and thus a hazard in PVC production.
Co-carcinogens are chemicals that do not necessarily cause cancer on their own, but promote the activity of other carcinogens in causing cancer.
After the carcinogen enters the body, the body makes an attempt to eliminate it through a process called biotransformation. The purpose of these reactions is to make the carcinogen more water-soluble so that it can be removed from the body. But these reactions can also convert a less toxic carcinogen into a more toxic carcinogen.
DNA is nucleophilic, therefore soluble carbon electrophiles are carcinogenic, because DNA attacks them. For example, some alkenes are toxicated by human enzymes to produce an electrophilic epoxide. DNA attacks the epoxide, and is bound permanently to it. This is the mechanism behind the carcinogenicity of benzo[a]pyrene in tobacco smoke, other aromatics, aflatoxin and mustard gas.
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 of 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.
Not all types of electromagnetic radiation are in fact carcinogenic. Low-energy waves on the electromagnetic spectrum are thought not to be including radio waves, microwave radiation, infrared radiation and visible light. There are many many documented cases of radar technicians experiencing prolonged exposure and a higher incidence of cancer. http://www.ncbi.nlm.nih.gov/pubmed/10926722 Higher-energy radiation, including ultraviolet radiation (present in sunlight), x-rays, and gamma radiation, generally is carcinogenic, if received in sufficient doses.
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.
Substances or foods irradiated with electrons or electromagnetic radiation (such as microwave, X-ray or gamma) are not carcinogenic. In contrast, non-electromagnetic neutron radiation produced inside nuclear reactors can produce secondary radiation through nuclear transmutation.
Cooking food at high temperatures, for example grilling or barbecuing meats, can 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). Charring of food resembles coking and tobacco pyrolysis, and produces similar 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.
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). Studies are underway at the FDA and European regulatory agencies to assess its potential risk to humans.
"Shiftwork that involves circadian disruption" was listed, in 2007, as a probable carcinogen by the World Health Organization's International Agency for Research on Cancer. (IARC Press release No. 180). Multiple studies have documented a link between night shift work and the increased incidence of breast cancer. Circadian disruption by exposure to light at night suppresses the production of the hormone melatonin which leads to reduction in cellular immune defense and surveillance necessary for protection from development of cancers. Melatonin also seems to have a direct protective effect against cancer, possibly in part because of its strong antioxidant properties.
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.
|Group 1||Cat. 1A||Known||A1||Cat. 1|
|Group 2A||Cat. 1B||Reasonably
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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 that have been highly influential in the classification of possible carcinogens.
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:
The National Toxicology Program of the U.S. Department of Health and Human Services is mandated to produce a biennial Report on Carcinogens. As of June 2011, the latest edition was the 12th report (2011). It classifies carcinogens into two groups:
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 wider assessment of the occupational hazards of chemicals.
This assessment scheme is being phased out in favor of the GHS scheme (see above), to which it is very close in category definitions.
Under a previous name, the NOHSC, in 1999 Safe Work Australia published the Approved Criteria for Classifying Hazardous Substances [NOHSC:1008(1999)]. Section 4.76 of this document outlines the criteria for classifying carcinogens as approved by the Australian government. This classification consists of three categories:
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 are carcinogenic.
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||
Not in widespread use, but found in:
|Beryllium and its compounds||
|Cadmium and its compounds|
|Hexavalent chromium(VI) compounds||
|Radon and its decay products||
|Shift work that involves|
|Involuntary smoking (Passive smoking)||
and other alpha particle
emitters with high atomic weight
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