Carcinogen

A carcinogen /kɑːrsɪnədʒən/ is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the 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 non-radioactive carcinogens are inhaled asbestos, certain dioxins, and tobacco smoke. Although the public generally associates carcinogenicity with synthetic chemicals, it is equally likely to arise from both natural and synthetic substances.^[1] Carcinogens are not necessarily immediately toxic; thus, their effect can be insidious.

Cigarettes have been known carcinogens for at least 65 years.

Carcinogens, as mentioned, are agents in the environment capable of contributing to cancer growth. Carcinogens can be categorized into two different types: activation-dependent and activation-independent, and each nature impacts their level and type of influence when it comes to promoting cancer growth.^[2] Activation-dependent carcinogens require metabolic activation or modification to induce cancer, while activation-independents ones do not. Examples of activation-dependent carcinogens^{[verification needed]} range from certain viruses, such as HPV,^[3] to consumed alcohol,^[4] to excessive amounts of red and processed meats,^[5] impacting a person's health in ways they may not immediately associate with cancer. Activation-independent carcinogens, such as ultraviolet rays or nitrosamines in tobacco products, possess characteristics enabling them to interact directly with DNA and other cellular components to cause harm. These include not requiring metabolic action or molecular changes to act, which complements their ability to be electrically excited, permitting them to interact with oxygen and nitrogen atoms in negatively charged cellular environments. This type of interaction leads to the alteration of DNA nucleotide bases, causing disarrangement of that genetic material. This disarrangement is also responsible for the formation of DNA adducts,^[6] segments of DNA which bind to carcinogens, which furthers harm. Eventually, failure in DNA repair mechanisms will lead to a buildup of DNA damage and potentially the development of cancer.^[6]

Cancer is any disease in which normal cells are damaged and do not undergo programmed cell death as fast as they divide via mitosis. Carcinogens may increase the risk of 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, severe DNA damage 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 virus 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. Other infectious organisms which cause cancer in humans include some bacteria (e.g. Helicobacter pylori ^[7][8]) and helminths (e.g. Opisthorchis viverrini ^[9] and Clonorchis sinensis^[10]).

Dioxins and dioxin-like compounds, benzene, kepone, EDB, and asbestos have all been classified as carcinogenic.^[11] As far back as the 1930s, industrial smoke and tobacco smoke were identified as sources of dozens of carcinogens, including benzo[a]pyrene, tobacco-specific nitrosamines such as nitrosonornicotine, and reactive aldehydes such as formaldehyde, 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 necessarily cause cancer on their own but promote the activity of other carcinogens in causing cancer.

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. However, in some cases, these reactions can also convert a less toxic carcinogen into a more toxic carcinogen.

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 carcinogenicity of benzo[a]pyrene in tobacco smoke, other aromatics, aflatoxin and mustard gas.

IUPAC definition

Carcinogenicity: Ability or tendency to produce cancer.

Note: In general, polymers are not known as carcinogens or mutagens,
however, residual monomers or additives [in polymers] can cause genetic mutations.^[12]

Radiation

Main article: radiation-induced cancer

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.^[13][14][15]

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.^[16]

Higher-energy radiation, including ultraviolet radiation (present in sunlight), x-rays, and gamma radiation, 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.^[17][18]

Substances or foods irradiated with electrons or electromagnetic radiation (such as microwave, X-ray or gamma) are not carcinogenic.^[19] In contrast, non-electromagnetic neutron radiation produced inside nuclear reactors can produce secondary radiation through nuclear transmutation.

In prepared food

See also: Cooking § Carcinogens, and Raw foodism

Chemicals used in processed and cured meat such as some brands of bacon, sausages and ham may produce carcinogens.^[20] 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.^[21] 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).^[22] 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.^[23]

Baking, grilling or broiling food, especially starchy foods, until a toasted crust is formed generates significant concentrations of acrylamide. 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".^[24]

In cigarettes

Main article: Tobacco and health

There is a strong association of smoking with lung cancer; the risk of developing lung cancer increases significantly in smokers.^[25] A large number of known carcinogens are found in cigarette smoke. Potent carcinogens found in cigarette smoke include polycyclic aromatic hydrocarbons (PAH, such as benzo(a)pyrene), benzene, and nitrosamine.^[26][27]

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.^[28]

Classification

Approximate equivalences
between classification schemes

IARC	GHS	NTP	ACGIH	EU
Group 1	Cat. 1A	Known	A1	Cat. 1A
Group 2A	Cat. 1B	Reasonably suspected	A2	Cat. 1B
Group 2B
	Cat. 2		A3	Cat. 2
Group 3
			A4
Group 4			A5

International Agency for Research on Cancer

The International Agency for Research on Cancer (IARC) is an intergovernmental agency established in 1965, which forms part of the World Health Organization of the United Nations. It is based in Lyon, France. Since 1971 it has published a series of Monographs on the Evaluation of Carcinogenic Risks to Humans^[29] that have been highly influential in the classification of possible carcinogens.

• Group 1: the agent (mixture) is definitely carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans. (Strongest tier for evidence of carcinogenity)
• Group 2A: the agent (mixture) is probably (product more likely to be) carcinogenic to humans. The exposure circumstance entails exposures that are probably carcinogenic to humans. (There is a bunch of data liking it to carcinogenicity, some may not link it to carcinogenicity)
• Group 2B: the agent (mixture) is possibly (chance of product being) carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans. (There is some data liking it to carcinogenicity)
• Group 3: the agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans. (A lack of data can make it fall into this category). Those could still be carcinogenic or not. This category might be seen as the "default (or initial) category"
• Group 4: the agent (mixture) is probably not carcinogenic to humans. (There is data mostly indicating [failing to find] that the mixture is carcinogenic).

Globally Harmonized System

The Globally Harmonized System of Classification and Labelling of Chemicals (GHS) is a United Nations initiative to attempt to harmonize the different systems of assessing chemical risk which currently exist (as of March 2009) around the world. It classifies carcinogens into two categories, of which the first may be divided again into subcategories if so desired by the competent regulatory authority:

• Category 1: known or presumed to have carcinogenic potential for humans
  • Category 1A: the assessment is based primarily on human evidence
  • Category 1B: the assessment is based primarily on animal evidence
• Category 2: suspected human carcinogens

U.S. National Toxicology Program

The National Toxicology Program of the U.S. Department of Health and Human Services is mandated to produce a biennial Report on Carcinogens.^[30] As of June 2011, the latest edition was the 12th report (2011).^[11] It classifies carcinogens into two groups:

• Known to be a human carcinogen
• Reasonably anticipated being a human carcinogen

American Conference of Governmental Industrial Hygienists

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. It assesses carcinogenicity as part of a wider assessment of the occupational hazards of chemicals.

• Group A1: Confirmed human carcinogen
• Group A2: Suspected human carcinogen
• Group A3: Confirmed animal carcinogen with unknown relevance to humans
• Group A4: Not classifiable as a human carcinogen
• Group A5: Not suspected as a human carcinogen

European Union

The European Union classification of carcinogens is contained in the Regulation (EC) No 1272/2008. It consists of three categories:^[31]

• Category 1A: Carcinogenic
• Category 1B: May cause cancer
• Category 2: Suspected of causing cancer

The former European Union classification of carcinogens was contained in the Dangerous Substances Directive and the Dangerous Preparations Directive. It also consisted of three categories:

• Category 1: Substances known to be carcinogenic to humans.
• Category 2: Substances which should be regarded as if they are carcinogenic to humans.
• Category 3: Substances which cause concern for humans, owing to possible carcinogenic effects but in respect of which the available information is not adequate for making a satisfactory assessment.

This assessment scheme is being phased out in favor of the GHS scheme (see above), to which it is very close in category definitions.

Safe Work Australia

Under a previous name, the NOHSC, in 1999 Safe Work Australia published the Approved Criteria for Classifying Hazardous Substances [NOHSC:1008(1999)].^[32] Section 4.76 of this document outlines the criteria for classifying carcinogens as approved by the Australian government. This classification consists of three categories:

• Category 1: Substances known to be carcinogenic to humans.
• Category 2: Substances that should be regarded as if they were carcinogenic to humans.
• Category 3: Substances that have possible carcinogenic effects in humans but about which there is insufficient information to make an assessment.

Common carcinogens

Occupational carcinogens

Occupational carcinogens are agents that pose a risk of cancer in several specific work-locations:

Disclaimer: The following list is far from being exhaustive.

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 mesothelioma	Not 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^[33]	Lung	Lightweight alloys Aerospace applications Nuclear reactors
Cadmium and its compounds^[34]	Prostate	Yellow pigments Phosphors Solders Batteries Metal paintings and coatings
Hexavalent chromium(VI) compounds	Lung	Paints Pigments Preservatives
Nitrosamines^[35]	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^[36]	Breast
Involuntary smoking (Passive smoking)^[37]	Lung
Radium-226, Radium-224, Plutonium-238, Plutonium-239^[38] 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:^[39]

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
• Alcohol (causing head and neck cancers)
• Other ionizing radiation (X-rays, gamma rays, etc.)
• Low refining or unrefined mineral oils
• Etc

Major carcinogens implicated in the four most common cancers worldwide

In this section, the carcinogens implicated as the main causative agents of the four most common cancers worldwide are briefly described. These four cancers are lung, breast, colon, and stomach cancers. Together they account for about 41% of worldwide cancer incidence and 42% of cancer deaths (for more detailed information on the carcinogens implicated in these and other cancers, see references^[40]).

Lung cancer

Lung cancer (pulmonary carcinoma) is the most common cancer in the world, both in terms of cases (1.6 million cases; 12.7% of total cancer cases) and deaths (1.4 million deaths; 18.2% of total cancer deaths).^[41] Lung cancer is largely caused by tobacco smoke. Risk estimates for lung cancer in the United States indicate that tobacco smoke is responsible for 90% of lung cancers. Other factors are implicated in lung cancer, and these factors can interact synergistically with smoking so that total attributable risk adds up to more than 100%. These factors include occupational exposure to carcinogens (about 9-15%), radon (10%) and outdoor air pollution (1-2%).^[42] Tobacco smoke is a complex mixture of more than 5,300 identified chemicals. The most important carcinogens in tobacco smoke have been determined by a "Margin of Exposure" approach.^[43] Using this approach, the most important tumorigenic compounds in tobacco smoke were, in order of importance, acrolein, formaldehyde, acrylonitrile, 1,3-butadiene, cadmium, acetaldehyde, ethylene oxide, and isoprene. Most of these compounds cause DNA damage by forming DNA adducts or by inducing other alterations in DNA.^{[citation needed]} DNA damages are subject to error-prone DNA repair or can cause replication errors. Such errors in repair or replication can result in mutations in tumor suppressor genes or oncogenes leading to cancer.

Breast cancer

Breast cancer is the second most common cancer [(1.4 million cases, 10.9%), but ranks 5th as cause of death (458,000, 6.1%)].^[41] Increased risk of breast cancer is associated with persistently elevated blood levels of estrogen.^[44] Estrogen appears to contribute to breast carcinogenesis by three processes; (1) the metabolism of estrogen to genotoxic, mutagenic carcinogens, (2) the stimulation of tissue growth, and (3) the repression of phase II detoxification enzymes that metabolize ROS leading to increased oxidative DNA damage.^[45][46][47] The major estrogen in humans, estradiol, can be metabolized to quinone derivatives that form adducts with DNA.^[48] 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.^[48] Genetic background, dietary practices and environmental factors also likely contribute to the incidence of DNA damage and breast cancer risk.

Colon cancer

Colorectal cancer is the third most common cancer [1.2 million cases (9.4%), 608,000 deaths (8.0%)].^[41] Tobacco smoke may be responsible for up to 20% of colorectal cancers in the United States.^[49] In addition, substantial evidence implicates bile acids as an important factor in colon cancer. Twelve studies (summarized in Bernstein et al.^[50]) indicate that the bile acids deoxycholic acid (DCA) or lithocholic acid (LCA) induce production of DNA-damaging reactive oxygen species or reactive nitrogen species in human or animal colon cells. Furthermore, 14 studies showed that DCA and LCA induce DNA damage in colon cells. Also 27 studies reported that bile acids cause programmed cell death (apoptosis). Increased apoptosis can result in selective survival of cells that are resistant to induction of apoptosis.^[50] Colon cells with reduced ability to undergo apoptosis in response to DNA damage would tend to accumulate mutations, and such cells may give rise to colon cancer.^[50] Epidemiologic studies have found that fecal bile acid concentrations are increased in populations with a high incidence of colon cancer. Dietary increases in total fat or saturated fat result in elevated DCA and LCA in feces and elevated exposure of the colon epithelium to these bile acids. When the bile acid DCA was added to the standard diet of wild-type mice invasive colon cancer was induced in 56% of the mice after 8 to 10 months.^[51] Overall, the available evidence indicates that DCA and LCA are centrally important DNA-damaging carcinogens in colon cancer.

Stomach cancer

Stomach cancer is the fourth most common cancer [990,000 cases (7.8%), 738,000 deaths (9.7%)].^[41] Helicobacter pylori infection is the main causative factor in stomach cancer. Chronic gastritis (inflammation) caused by H. pylori is often long-standing if not treated. Infection of gastric epithelial cells with H. pylori results in increased production of reactive oxygen species (ROS).^[52][53] ROS cause oxidative DNA damage including the major base alteration 8-hydroxydeoxyguanosine (8-OHdG). 8-OHdG resulting from ROS is increased in chronic gastritis. The altered DNA base can cause errors during DNA replication that have mutagenic and carcinogenic potential. Thus H. pylori-induced ROS appear to be the major carcinogens in stomach cancer because they cause oxidative DNA damage leading to carcinogenic mutations. Diet is thought to be a contributing factor in stomach cancer - in Japan where very salty pickled foods are popular, the incidence of stomach cancer is high. Preserved meat such as bacon, sausages, and ham increases the risk while a diet high in fresh fruit and vegetables may reduce the risk. The risk also increases with age.^[54]

See also

• History of cancer
• Mutagen
• Possible carcinogen
• Safe handling of carcinogens
• Teratogen

References

1. Ames BN, Gold LS (January 2000). "Paracelsus to parascience: the environmental cancer distraction". Mutation Research. 447 (1): 3–13. doi:10.1016/S0027-5107(99)00194-3. PMID 10686303.
2. editor., Poirier, M. C. (Miriam C.) (28 September 2018). Carcinogens, DNA damage and cancer risk : mechanisms of chemical carcinogenesis. ISBN 978-981-323-719-3. OCLC 1086736058. {{cite book}}: |last= has generic name (help)
3. Cosper, Pippa F.; Bradley, Samantha; Luo, Qianyun; Kimple, Randall J. (October 2021). "Biology of HPV Mediated Carcinogenesis and Tumor Progression". Seminars in Radiation Oncology. 31 (4): 265–273. doi:10.1016/j.semradonc.2021.02.006. ISSN 1053-4296. PMC 8409095. PMID 34455982.
4. Rehm, Jürgen; Shield, Kevin D.; Weiderpass, Elisabete (2020-11-01). "Alcohol consumption. A leading risk factor for cancer". Chemico-Biological Interactions. 331: 109280. doi:10.1016/j.cbi.2020.109280. ISSN 0009-2797. PMID 33010221. S2CID 222154741.
5. Huang, Yin; Cao, Dehong; Chen, Zeyu; Chen, Bo; Li, Jin; Guo, Jianbing; Dong, Qiang; Liu, Liangren; Wei, Qiang (2021-09-15). "Red and processed meat consumption and cancer outcomes: Umbrella review". Food Chemistry. 356: 129697. doi:10.1016/j.foodchem.2021.129697. ISSN 0308-8146. PMID 33838606.
6. Barnes, Jessica L.; Zubair, Maria; John, Kaarthik; Poirier, Miriam C.; Martin, Francis L. (2018). "Carcinogens and DNA damage". Biochemical Society Transactions. 46 (5): 1213–1224. doi:10.1042/bst20180519. PMC 6195640. PMID 30287511. Retrieved 2022-09-26.
7. Hatakeyama M, Higashi H (December 2005). "Helicobacter pylori CagA: a new paradigm for bacterial carcinogenesis". Cancer Science. 96 (12): 835–843. doi:10.1111/j.1349-7006.2005.00130.x. PMID 16367902.
8. González CA, Sala N, Rokkas T (September 2013). "Gastric cancer: epidemiologic aspects". Helicobacter. 18 Suppl 1 (Supplement 1): 34–38. doi:10.1111/hel.12082. PMID 24011243. S2CID 22918077.
9. Sripa B, Kaewkes S, Sithithaworn P, Mairiang E, Laha T, Smout M, et al. (July 2007). "Liver fluke induces cholangiocarcinoma". PLOS Medicine. 4 (7): e201. doi:10.1371/journal.pmed.0040201. PMC 1913093. PMID 17622191.
10. Rustagi T, Dasanu CA (June 2012). "Risk factors for gallbladder cancer and cholangiocarcinoma: similarities, differences and updates". Journal of Gastrointestinal Cancer. 43 (2): 137–147. doi:10.1007/s12029-011-9284-y. PMID 21597894. S2CID 31590872.
11. Report on Carcinogens, Eleventh Edition April 20, 2009, at the Wayback Machine; U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program (2011).
12. Vert M, Doi Y, Hellwich KH, Hess M, Hodge P, Kubisa P, et al. (2012). (PDF). Pure and Applied Chemistry. 84 (2): 377–410. doi:10.1351/PAC-REC-10-12-04. S2CID 98107080. Archived from the original (PDF) on 2015-03-19. Retrieved 2013-07-14.
13. Acharya PV (January 1975). The effect of ionizing radiation on the formation of age-correlated oligo deoxyribo nucleo phospheryl peptides in mammalian cells. 10th International Congress of Gerontology. Jerusalem.
14. Acharya PV (July 1976). Implications of The Action of Low-Level Ionizing Radiation on the Inducement of Irreparable DNA Damage Leading to Mammalian Aging and Chemical Carcinogenesis. 10th International Congress of Biochemistry. Hamburg, Germany.
15. Acharya PV (April 1977). Irreparable DNA-Damage by Industrial Pollutants in Pre-mature Aging, Chemical Carcinogenesis, and Cardiac Hypertrophy: Experiments and Theory. 1st International Meeting of Heads of Clinical Biochemistry Laboratories. Jerusalem, Israel.
16. Richter E, Berman T, Ben-Michael E, Laster R, Westin JB (2000). "Cancer in radar technicians exposed to radiofrequency/microwave radiation: sentinel episodes". International Journal of Occupational and Environmental Health. 6 (3): 187–193. doi:10.1179/oeh.2000.6.3.187. PMID 10926722. S2CID 25147479.
17. . Archived from the original on 2012-08-10. Retrieved 2010-07-02.
18. "Skin-tone gene could predict cancer risk".
19. Center for Food Safety and Applied Nutrition (20 April 2020). "Food Irradiation: What You Need to Know". FDA. Retrieved 20 January 2021.
20. "Processed meats do cause cancer - WHO". BBC. 26 October 2015.
21. Scanlan RA (May 1983). "Formation and occurrence of nitrosamines in food". Cancer Research. 43 (5 Suppl): 2435s–2440s. PMID 6831466.
22. Zheng W, Gustafson DR, Sinha R, Cerhan JR, Moore D, Hong CP, et al. (November 1998). "Well-done meat intake and the risk of breast cancer". Journal of the National Cancer Institute. 90 (22): 1724–1729. doi:10.1093/jnci/90.22.1724. PMID 9827527.
23. "National Cancer Institute, 2004 analysis and recommendations". Cancer.gov. 2004-09-15. Retrieved 2010-09-22.
24. "Can eating burnt foods cause cancer?". Cancer Research UK. 15 October 2021.
25. Villeneuve PJ, Mao Y (1994). "Lifetime probability of developing lung cancer, by smoking status, Canada". Canadian Journal of Public Health. 85 (6): 385–388. PMID 7895211.
26. "Harms of Cigarette Smoking and Health Benefits of Quitting". National Cancer Institute. 2017-12-21.
27. Tomar RC, Beaumont J, Hsieh JC (August 2009). "Evidence on the carcinogenicity of marijuana smoke" (PDF). Reproductive and Cancer Hazard Assessment Branch Office of Environmental Health Hazard Assessment, California Environmental Protection Agency. Retrieved 23 June 2012.
28. "The Gale Encyclopedia of Cancer: A guide to Cancer and its Treatments, Second Edition. Page no. 137".
29. "IARC Monographs". Monographs.iarc.fr. Retrieved 2010-09-22.
30. Section 301(b)(4) of the Public Health Service Act, as amended by Section 262, Pub. L. 95–622.
31. (PDF). European Chemicals Agency. May 2012. Archived from the original (PDF) on 2021-02-24. Retrieved 2020-11-03.
32. Safe Work Australia 2010-12-01 at the Wayback Machine, NOHSC. (1999). Approved criteria for classifying hazardous substances [NOHSC:1008(1999)] § 4.76. Accessed 21/05/2011
33. Beyersmann D, Hartwig A (August 2008). "Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms". Archives of Toxicology. 82 (8): 493–512. doi:10.1007/s00204-008-0313-y. PMID 18496671. S2CID 25513051.
34. Hartwig A (2013). "Chapter 15. Cadmium and cancer". In Sigel A, Sigel H, Sigel RK (eds.). Cadmium: From Toxicology to Essentiality. Metal Ions in Life Sciences. Vol. 11. Springer. pp. 491–507. doi:10.1007/978-94-007-5179-8_15. ISBN 978-94-007-5178-1. PMID 23430782.
35. Tricker AR, Preussmann R (1991). "Carcinogenic N-nitrosamines in the diet: occurrence, formation, mechanisms and carcinogenic potential". Mutation Research. 259 (3–4): 277–289. doi:10.1016/0165-1218(91)90123-4. PMID 2017213.
36. . Archived from the original on 2011-07-21. Retrieved 2011-07-01.
37. Tobacco Smoke and Involuntary Smoking 2015-03-15 at the Wayback Machine, IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 83 (2004).
38. Survival, causes of death, and estimated tissue doses in a group of human beings injected with plutonium, 751053, R. E. Rowland and Patricia W. Durbin, 1975.
39. Mitchell RS, Kumar V, Abbas AK, Fausto N (2007). Robbins Basic Pathology (8th ed.). Philadelphia: Saunders. ISBN 978-1-4160-2973-1. Table 6-2
40. Bernstein H, Payne CM, Bernstein C, Garewal H, Dvorak K (2008). . In Kimura H, Suzuki A (eds.). New Research on DNA Damages. New York: Nova Science Publishers, Inc. pp. 1–47. ISBN 978-1604565812. Archived from the original on 2014-10-25.
41. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (December 2010). "Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008". International Journal of Cancer. 127 (12): 2893–2917. doi:10.1002/ijc.25516. PMID 21351269. S2CID 23583962.
42. Alberg AJ, Ford JG, Samet JM (September 2007). "Epidemiology of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition)". Chest. 132 (3 Suppl): 29S–55S. doi:10.1378/chest.07-1347. PMID 17873159.
43. Cunningham FH, Fiebelkorn S, Johnson M, Meredith C (November 2011). "A novel application of the Margin of Exposure approach: segregation of tobacco smoke toxicants". Food and Chemical Toxicology. 49 (11): 2921–2933. doi:10.1016/j.fct.2011.07.019. PMID 21802474.
44. Yager JD, Davidson NE (January 2006). "Estrogen carcinogenesis in breast cancer". The New England Journal of Medicine. 354 (3): 270–282. doi:10.1056/NEJMra050776. PMID 16421368.
45. Ansell PJ, Espinosa-Nicholas C, Curran EM, Judy BM, Philips BJ, Hannink M, Lubahn DB (January 2004). "In vitro and in vivo regulation of antioxidant response element-dependent gene expression by estrogens". Endocrinology. 145 (1): 311–317. doi:10.1210/en.2003-0817. PMID 14551226.
46. Belous AR, Hachey DL, Dawling S, Roodi N, Parl FF (January 2007). "Cytochrome P450 1B1-mediated estrogen metabolism results in estrogen-deoxyribonucleoside adduct formation". Cancer Research. 67 (2): 812–817. doi:10.1158/0008-5472.CAN-06-2133. PMID 17234793.
47. Bolton JL, Thatcher GR (January 2008). "Potential mechanisms of estrogen quinone carcinogenesis". Chemical Research in Toxicology. 21 (1): 93–101. doi:10.1021/tx700191p. PMC 2556295. PMID 18052105.
48. Yue W, Santen RJ, Wang JP, Li Y, Verderame MF, Bocchinfuso WP, et al. (September 2003). "Genotoxic metabolites of estradiol in breast: potential mechanism of estradiol induced carcinogenesis". The Journal of Steroid Biochemistry and Molecular Biology. 86 (3–5): 477–486. doi:10.1016/s0960-0760(03)00377-7. PMID 14623547. S2CID 31885800.
49. Giovannucci E, Martínez ME (December 1996). "Tobacco, colorectal cancer, and adenomas: a review of the evidence". Journal of the National Cancer Institute. 88 (23): 1717–1730. doi:10.1093/jnci/88.23.1717. PMID 8944002.
50. Bernstein H, Bernstein C, Payne CM, Dvorak K (July 2009). "Bile acids as endogenous etiologic agents in gastrointestinal cancer". World Journal of Gastroenterology. 15 (27): 3329–3340. doi:10.3748/wjg.15.3329. PMC 2712893. PMID 19610133.
51. Bernstein C, Holubec H, Bhattacharyya AK, Nguyen H, Payne CM, Zaitlin B, Bernstein H (August 2011). "Carcinogenicity of deoxycholate, a secondary bile acid". Archives of Toxicology. 85 (8): 863–871. doi:10.1007/s00204-011-0648-7. PMC 3149672. PMID 21267546.
52. Ding SZ, Minohara Y, Fan XJ, Wang J, Reyes VE, Patel J, et al. (August 2007). "Helicobacter pylori infection induces oxidative stress and programmed cell death in human gastric epithelial cells". Infection and Immunity. 75 (8): 4030–4039. doi:10.1128/IAI.00172-07. PMC 1952011. PMID 17562777.
53. Handa O, Naito Y, Yoshikawa T (2011). "Redox biology and gastric carcinogenesis: the role of Helicobacter pylori". Redox Report. 16 (1): 1–7. doi:10.1179/174329211X12968219310756. PMC 6837368. PMID 21605492.
54. "Stomach cancer risks and causes". Cancer Research UK.

External links

 

Look up carcinogen in Wiktionary, the free dictionary.

 

Wikimedia Commons has media related to Carcinogens.

• CDC – Occupational Cancer – Carcinogen List – NIOSH Safety and Health Topic
• Recognized Carcinogens 2007-12-17 at the Wayback Machine
• Database of Rodent Carcinogens
• Comparing Possible Cancer Hazards from Human Exposures to Rodent Carcinogens