Carcinogen

Common carcinogens; clockwise from top left: tobacco smoking, alcoholic beverages, asbestos, ultraviolet radiation

A carcinogen (/kɑːrˈsɪnədʒən/) is any agent that promotes the development of cancer.^[1] 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.^[2] Most carcinogens act by creating mutations in DNA that disrupt a cell's normal processes for regulating growth, leading to uncontrolled cellular proliferation.^[1] 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.^[2]

The specific mechanisms for carcinogenic activity is unique to each agent and cell type. Carcinogens can be broadly categorized, however, as activation-dependent and activation-independent which relate to the agent's ability to engage directly with DNA.^[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.^[4] 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.^[3] Examples of activation-independent carcinogens include ultraviolet light, ionizing radiation and alkylating agents.^[4]

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.^[5] For blood cancers, the latency period may be as short as two.^[5] 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.^[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.^[10] According to NIOSH, 3-6% of cancers worldwide are due to occupational exposures.^[5] 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.