A carcinogen () is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruses and bacteria. Most carcinogens act by creating mutations in DNA that disrupt a cell's normal processes for regulating growth, leading to uncontrolled cellular proliferation. This occurs when the cell's DNA repair processes fail to identify DNA damage, allowing the defect to be passed down to daughter cells. The damage accumulates over time. This is typically a multi-step process during which the regulatory mechanisms within the cell are gradually dismantled allowing for unchecked cellular division.
The specific mechanisms for carcinogenic activity are unique to each agent and cell type. Carcinogenic agents can be broadly categorized, however, as either activation-dependent or activation-independent, which relate to the agent's ability to engage directly with DNA. Activation-dependent agents are relatively inert in their original form, but are bioactivated in the body into metabolites or intermediaries capable of damaging human DNA. These are also known as "indirect-acting" carcinogens. Examples of activation-dependent carcinogens include polycyclic aromatic hydrocarbons (PAHs), heterocyclic aromatic amines, and mycotoxins.
Activation-independent carcinogens, or "direct-acting" carcinogens, are those that are capable of directly damaging DNA without any modification to their molecular structure. These agents typically include electrophilic groups that react readily with the net negative charge of DNA molecules. Examples of activation-independent carcinogens include ultraviolet light, ionizing radiation and alkylating agents.
The time from exposure to a carcinogen to the development of cancer is known as the latency period. For most solid tumors in humans, the latency period is between 10 and 40 years depending on cancer type. For blood cancers, the latency period may be as short as two. Due to prolonged latency periods identification of carcinogens can be challenging.
A number of organizations review and evaluate the cumulative scientific evidence regarding the potential carcinogenicity of specific substances. Foremost among these is the International Agency for Research on Cancer (IARC). IARC routinely publishes monographs in which specific substances are evaluated for their potential carcinogenicity to humans and subsequently categorized into one of four groupings: Group 1: Carcinogenic to humans, Group 2A: Probably carcinogenic to humans, Group 2B: Possibly carcinogenic to humans and Group 3: Not classifiable as to its carcinogenicity to humans. Other organizations that evaluate the carcinogenicity of substances include the National Toxicology Program of the US Public Health Service, NIOSH, the American Conference of Governmental Industrial Hygienists and others.
There are numerous sources of exposures to carcinogens including ultraviolet radiation from the sun, radon gas emitted in residential basements, environmental contaminants such as chlordecone, cigarette smoke and ingestion of some types of foods such as alcohol and processed meats. Occupational exposures represent a major source of carcinogens with an estimated 666,000 annual fatalities worldwide attributable to work related cancers. According to NIOSH, 3-6% of cancers worldwide are due to occupational exposures. Well established occupational carcinogens include vinyl chloride and hemangiosarcoma of the liver, benzene and leukemia, aniline dyes and bladder cancer, asbestos and mesothelioma, polycyclic aromatic hydrocarbons and scrotal cancer among chimney sweeps to name a few.
Radiation
Ionizing Radiation 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.
Non-ionizing radiation 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.
Higher-energy radiation, including ultraviolet radiation (present in sunlight), 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.
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.
Common carcinogens associated with food Alcohol
Alcohol is a carcinogen of the head and neck, esophagus, liver, colon and rectum, and breast. It has a synergistic effect with tobacco smoke in the development of head and neck cancers. In the United States approximately 6% of cancers and 4% of cancer deaths are attributable to alcohol use.
Processed meats Chemicals used in processed and cured meat such as some brands of bacon, sausages and ham may produce carcinogens. 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.
Meats cooked at high temperatures
Cooking food at high temperatures, for example grilling or barbecuing meats, may 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). 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.
Acrylamide in foods Frying, grilling or broiling food at high temperatures, especially starchy foods, until a toasted crust is formed generates acrylamides. This discovery in 2002 led to international health concerns. Subsequent research has however found that it is not likely that the acrylamides in burnt or well-cooked food cause cancer in humans; Cancer Research UK categorizes the idea that burnt food causes cancer as a "myth".
Biologic agents Several biologic agents are known carcinogens.
Aflatoxin B1, a toxin produced by the fungus Aspergillus flavus which is a common contaminant of stored grains and nuts, is a known cause of hepatocellular cancer. The bacteria H. pylori is known to cause stomach cancer and MALT lymphoma. Hepatitis B and C are associated with the development of hepatocellular cancer. HPV is the primary cause of cervical cancer.
Cigarette smoke
Tobacco smoke contains at least 70 known carcinogens and is implicated in the development of numerous types of cancers including cancers of the lung, larynx, esophagus, stomach, kidney, pancreas, liver, bladder, cervix, colon, rectum and blood. Potent carcinogens found in cigarette smoke include polycyclic aromatic hydrocarbons (PAH, such as benzo(a)pyrene), benzene, and nitrosamine.
Occupational carcinogens Given that populations of workers are more likely to have consistent, often high level exposures to chemicals rarely encountered in normal life, much of the evidence for the carcinogenicity of specific agents is derived from studies of workers.
+ Selected carcinogens 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 mesotheliomaNot 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 commodity chemical Beryllium and its compounds Lung Lightweight alloys Aerospace applications Nuclear reactors Cadmium and its compounds Prostate Yellow pigments Phosphors Solders Batteries Metal paintings and coatings Hexavalent chromium(VI) compounds Lung Paints Pigments Preservatives Nitrosamines Lung Esophagus Liver cigarette smoke nitrite-treated foods (cured meats) Ethylene oxide Leukemia commodity chemical 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 Production of polyvinyl chloride Shift work that involves circadian disruption Breast Involuntary smoking (Passive smoking) Lung Radium-226, Radium-224, Plutonium-238, Plutonium-239 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:
Others Gasoline (contains aromatics) Lead and its compounds Alkylating antineoplastic agents (e.g., mechlorethamine) Styrene Other alkylating agents (e.g., dimethyl sulfate) Ultraviolet radiation from the sun and UV lamps Other ionizing radiation (X-rays, gamma rays, etc.) Low refining or unrefined mineral oils
Mechanisms of carcinogenicity 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.
Classification + Approximate equivalencesbetween classification schemes IARC GHS NTP ACGIH EU Group 1 Cat. 1A Known A1 Cat. 1A Group 2A Cat. 1B Reasonablysuspected A2 Cat. 1B Group 2B Cat. 2 A3 Cat. 2 Group 3 A4 Group 4 A5
International Agency for Research on Cancer