[2] Most carcinogens act by creating mutations in DNA that disrupt a cell's normal processes for regulating growth, leading to uncontrolled cellular proliferation.
This is typically a multi-step process during which the regulatory mechanisms within the cell are gradually dismantled allowing for unchecked cellular division.
[3] 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 agents typically include electrophilic groups that react readily with the net negative charge of DNA molecules.
A number of organizations review and evaluate the cumulative scientific evidence regarding the potential carcinogenicity of specific substances.
[6] 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.
[7] There are numerous sources of exposures to carcinogens including ultraviolet radiation from the sun, radon gas[8] emitted in residential basements, environmental contaminants such as chlordecone, cigarette smoke and ingestion of some types of foods such as alcohol and processed meats.
[9] Occupational exposures represent a major source of carcinogens with an estimated 666,000 annual fatalities worldwide attributable to work related cancers.
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.
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.
[19] 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.
[20] 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).
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.
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.
[25] Potent carcinogens found in cigarette smoke include polycyclic aromatic hydrocarbons (PAH, such as benzo(a)pyrene), benzene, and nitrosamine.
[38] 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.
This classification consists of three categories: In this section, the carcinogens implicated as the main causative agents of the four most common cancers worldwide are briefly described.
[49] These derivatives can cause depurination, 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.
[49] Genetic background, dietary practices and environmental factors also likely contribute to the incidence of DNA damage and breast cancer risk.
[52] Epidemiologic studies have found that fecal bile acid concentrations are increased in populations with a high incidence of colon cancer.
Infection of gastric epithelial cells with H. pylori results in increased production of reactive oxygen species (ROS).