Carcinogens

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The term carcinogen refers to any substance, radionuclide or radiation that is an agent directly involved in the promotion of cancer or in the facilitation of its propagation. This may be due to 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 carcinogens are, inhaled asbestos, certain dioxins, and tobacco smoke.

Cancer is a disease where damaged cells of the patient's body do not undergo programmed cell death, but their growth is no longer controlled and their metabolism is altered. Carcinogens may increase the risk of getting 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 DNA damage, if too severe to repair, leads to programmed cell death, 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 viruses 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.

Benzene, kepone, EDB, asbestos, and the waste rock of oil shale mining 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 benzopyrene, tobacco-specific nitrosamines such as nitrosonornicotine, and reactive aldehydes such as formaldehyde &mdash; 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 separately cause cancer, but do so in specific combinations.

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 one.

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 carcinogenity of benzopyrene in tobacco smoke, other aromatics, aflatoxin and mustard gas.

Radiation
CERCLA identifies all radionuclides as carcinogens, although the nature of the emitted radiation (alpha, beta, or gamma, and the energy), its consequent capacity to cause ionization in tissues, and the magnitude of radiation exposure, determine the potential hazard. Carcinogenity 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 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. Marie Curie, one of the pioneers of radioactivity, died of cancer caused by radiation exposure during her experiments.

Not all types of electromagnetic radiation are carcinogenic. Low-energy waves on the electromagnetic spectrum are generally not, including radio waves, microwave radiation, infrared radiation, and visible light. Higher-energy radiation, including ultraviolet radiation (present in sunlight), x-rays, and gamma radiation, generally is carcinogenic, if received in sufficient doses.

Substances or foods irradiated with electrons or electromagnetic radiation (such as microwave, X-ray or gamma) are not carcinogenic. No "radiation" remains, just like no light remains in a lens. (In contrast, non-electromagnetic neutron radiation produced inside nuclear reactors can make substances radioactive.)

Carcinogens in prepared food
Cooking food at high temperatures, for example broiling 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., benzopyrene). 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 broiling shortens the time on the hot pan, which can help minimize the formation of these carcinogens.

Reports from the Food Standards Agency have found that the known animal carcinogen 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. The charred residue on barbecued meats has been identified as a carcinogen, along with many other tars.

Nevertheless, the fact that the food contains minute quantities does not necessarily mean that there is a significant hazard. The gastrointestinal tract sheds its outer layer continuously to protect itself from carcinomas, and has a high activity of detoxifying enzymes.

Classification of carcinogens
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 (MNU) 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.

IARC classification of carcinogens
Further details can be found in the IARC Monographs.
 * 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.

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