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A carcinogen is defined as any substance or radiation that promotes cancer formation or carcinogenesis. Chemical carcinogens may be natural or synthetic, toxic or non-toxic. Many carcinogens are organic in nature, such as benzoapyrene and viruses. An example of carcinogenic radiation is ultraviolet light.
How Carcinogens Work
Carcinogens prevent normal cell death (apoptosis) from occurring so cellular division is uncontrolled. This results in a tumor. If the tumor develops the ability to spread or metastasize (becomes malignant), cancer results. Some carcinogens damage DNA, however, if significant genetic damage occurs, usually a cell simply dies. Carcinogens alter cellular metabolism in other ways, causing affected cells to become less specialized and either masking them from the immune system or else preventing the immune system from killing them.
Everyone is exposed to carcinogens every day, yet not every exposure leads to cancer. The body uses several mechanisms to remove carcinogens or repair/remove damaged cells:
- Cells recognize many carcinogens and attempt to render them harmless through biotransformation. Biotransformation increases the solubility of a carcinogen in water, making it easier to flush from the body. However, sometimes biotransformation increases the carcinogenicity of a chemical.
- DNA repair genes fix damaged DNA before it can replicate. Usually, the mechanism works, but sometimes the damage isn't fixed or is too extensive for the system to repair.
- Tumor suppressor genes ensure cell growth and division behave normally. If a carcinogen affects a proto-oncogene (gene involved in normal cell growth), the change can allow cells to divide and live when they ordinarily wouldn't. Genetic changes or hereditary predisposition play a role in carcinogen activity.
Examples of Carcinogens
Radionuclides are carcinogens, whether or not they are toxic, because they emit alpha, beta, gamma, or neutron radiation that can ionize tissues. Many types of radiation are carcinogenic, such as ultraviolet light (including sunlight), x-rays, and gamma rays. Usually, microwaves, radio waves, infrared light, and visible light are not considered carcinogenic because the photons don't have enough energy to break chemical bonds. However, there are documented cases of usually "safe" forms of radiation being associated with increased cancer rate with prolonged high-intensity exposure. Foods and other materials that have been irradiated with electromagnetic radiation (e.g., x-rays, gamma rays) are not carcinogenic. Neutron irradiation, in contrast, can make substances carcinogenic through secondary radiation.
Chemical carcinogens include carbon electrophiles, which attack DNA. Examples of carbon electrophiles are mustard gas, some alkenes, aflatoxin, and benzoapyrene. Cooking and processing foods can produce carcinogens. Grilling or frying food, in particular, can produce carcinogens such as acrylamide (in french fries and potato chips) and polynuclear aromatic hydrocarbons (in grilled meat). Some of the main carcinogens in cigarette smoke are benzene, nitrosamine, and polycyclic aromatic hydrocarbons (PAHs). Many of these compounds are found in other smoke, too. Other important chemical carcinogens are formaldehyde, asbestos, and vinyl chloride.
Natural carcinogens include aflatoxins (found in grains and peanuts), the hepatitis B and human papillomaviruses, the bacteria Helicobacter pylori, and the liver flukes Clonorchis sinensis and Oposthorchis veverrini.
How Carcinogens Are Classified
There are many different systems of classifying carcinogens, generally based on whether a substance is known to be carcinogenic in humans, a suspected carcinogen, or a carcinogen in animals. Some classification systems also allow for labeling a chemical as unlikely to be a human carcinogen.
One system is that used by the International Agency for Research on Cancer (IARC), which is part of the World Health Organization (WHO).
- Group 1: known human carcinogen, likely to cause cancer under typical exposure circumstances
- Group 2A: probably a human carcinogen
- Group 2B: possibly a human carcinogen
- Group 3: not classifiable
- Group 4: probably not a human carcinogen
Carcinogens may be categorized according to the type of damage they cause. Genotoxins are carcinogens that bind to DNA, mutate it, or cause irreversible damage. Examples of genotoxins include ultraviolet light, other ionizing radiation, some viruses, and chemicals such as N-nitroso-N-methylurea (NMU). Nongenotoxins don't damage DNA, but they promote cell growth and/or prevent programmed cell death. Examples of nongenotoxic carcinogens are some hormones and other organic compounds.
How Scientists Identify Carcinogens
The only certain way to know whether a substance is a carcinogen is to expose people to it and see if they develop cancer. Obviously, this is neither ethical nor practical, so most carcinogens are identified in other ways. Sometimes an agent is predicted to cause cancer because it has a similar chemical structure or effect on cells as a known carcinogen. Other studies are conducted on cell cultures and lab animals, using much higher concentrations of chemicals/viruses/radiation than a person would encounter. These studies identify "suspected carcinogens" because the action in animals may be different in humans. Some studies use epidemiological data to find trends in human exposure and cancer.
Procarcinogens and Co-carcinogens
Chemicals that are not carcinogenic, but become carcinogens when they are metabolized in the body are called procarcinogens. An example of a procarcinogen is nitrite, which is metabolized to form carcinogenic nitrosamines.
A co-carcinogen or promoter is a chemical that doesn't cause cancer on its own but promotes carcinogen activity. The presence of both chemicals together increases the likelihood of carcinogenesis. Ethanol (grain alcohol) is an example of a promoter.