Carcinogen

The International Agency for the Study of Cancer WHO has identified four groups of substances for their carcinogenic properties ^{[4] [5]} :

1. carcinogenic to humans, there are 120 of them,
2. probably and possibly carcinogenic - 82 and 311,
3. unclassified as carcinogenic for humans - 499,
4. non-carcinogenic - 1.

The International Agency for Research on Cancer placed in the fourth group the only substance with proven non-carcinogenicity — Caprolactam ^{[4] [6]}

Among the chemical carcinogens, the most common are:

• Nitrates and nitrites . Nitrites enter the body with food (in small quantities they are found in cereals and root crops , as well as in meat products , where they are added as preservatives ). The main source of nitrates in the body is vegetables grown under conditions of excessive use of nitrogen fertilizers . Part of the nitrates during storage of food or directly in the digestive tract can be restored to nitrite. Once in the stomach, nitrites can under the action of gastric juice turn into nitrosamines - substances with a wide range of carcinogenic effects ^{[7] [8]} .
• Nutritional Supplements Some food additives (for example: E123-Amaranth (not to be confused with amaranth ), E121-Citrus red 2 ) are proven carcinogenic and prohibited by law in many countries.
• Polycyclic aromatic hydrocarbons and their derivatives - are formed during the combustion of household waste, incomplete combustion of petroleum products and are present in the exhaust gases of cars. Among them are extremely carcinogenic substances, hundreds of times more dangerous than benzene . Some can be formed when frying food, cooking vegetable oils .
• Benzpyrene - formed during frying and cooking on a spit. There are many of them in tobacco smoke. The products of protein pyrolysis are formed by prolonged heating of meat in the oven. Also found in the products of pyrolysis of wood and some other organic products. .
• Peroxides - are formed in rancid fats and with strong heating of vegetable oils. .
• Aflatoxins are deadly mycotoxins (a subclass of polyketids ). These fungi are produced by mold fungi - micromycetes of several species of the genus Aspergillus ( Aspergillus ), in particular Aspergillus flavus (hence the name aflatoxins) and Aspergillus parasiticus , which grow and infect grains, seeds and fruits of plants with a high content of vegetable oils and fatty acids (for example, , on seeds of a peanut, oil-bearing crops) and other substrates. Among all biologically produced poisons, aflatoxins are the strongest hepatocarcinogens found to date ^[9] .
• Dioxins - organochlorine compounds produced by burning household garbage .
• Vinyl chloride - a substance is extremely flammable and explosive. Its combustion products are toxic. It has a carcinogenic, mutagenic and teratogenic effect on the human body ^{[9] [10]} .

• Benzene is a toxic and carcinogenic substance ^[9] . Benzene vapors can penetrate intact skin. If the human body is exposed to prolonged exposure to benzene in low concentrations, the consequences can also be very serious. In this case, chronic benzene poisoning can cause leukemia (blood cancer) and anemia (lack of hemoglobin in the blood) .
• Formaldehyde is toxic and has a strong negative effect on the central nervous system . Formaldehyde is listed as a carcinogen of GN 1.1.725-98 in the “probably carcinogenic for humans” section, and its carcinogenicity for animals has been proven ^{[11] [12] [13]} .
• Cadmium - cumulative poison (able to accumulate in the body to the amount of hazardous to health). Carcinogenic ^[14] . Cadmium compounds are poisonous.
• Arsenic is a toxic and carcinogenic substance ^[9] . All arsenic compounds are also poisonous.
• Hexavalent chromium is a recognized carcinogen by inhalation ^[15] .
• Nickel - Nickel compounds are toxic, carcinogenic, allergenic , mutagenic .
• Asbestos - stands alone among carcinogens ^[9] . It is difficult to attribute to chemical carcinogens, which, as a rule, are chemically active substances. Asbestos carcinogenicity, on the contrary, is expressed in the fact that a living organism is not able to get rid of microscopic, chemically extremely inert, particles of this substance.

Mechanism of action of chemical carcinogens

Most chemical carcinogens are organic compounds , only a small number of inorganic substances have this ability. According to Miller, all carcinogens to some extent are electrophiles , which easily interact with the nucleophilic groups of the nitrogenous bases of nucleic acids, in particular DNA , forming strong covalent bonds with them ^[16] . The negative effects of carcinogens are manifested in the chemical modification of nucleic acid. The consequences of such a modification are manifested in the impossibility of the proper running of the processes of transcription and DNA replication , the cause of which is the formation of the so-called DNA adducts covalently associated with it. For example, when replicating modified DNA, the nucleotides of which are associated with a carcinogen, can be incorrectly read by DNA polymerase , as a result of which mutations occur. The accumulation of a large number of mutations in the genome leads to the transformation of a normal cell into a tumor cell, which is the basis of carcinogenesis .

Chemical carcinogens can be divided into two large groups:

• Genotoxic
• Non-genotoxic

Genotoxic carcinogens are chemical compounds that, when they interact with components of DNA, may cause damage and mutations in the cell genome. Mutations, in turn, can lead to cell transformation processes, that is, to the formation of tumor cells.

Non-genotoxic carcinogens are chemicals that can cause damage to the genome only in high concentrations, with very long and almost uninterrupted exposure. They cause uncontrolled cell proliferation , inhibit apoptosis , disrupt the interaction between cells ( cell adhesion ). Most non-genotoxic carcinogens are promoters of carcinogenesis, such as: organochlorine pesticides , hormones , fibrous materials, asbestos , especially its dust.

According to the method of action, genotoxic carcinogens can be divided into:

• straight lines are highly reactive substances that directly form covalently bound adducts with DNA (these are alkylating and acetylating substances — N-nitrosylalkyl urea (HAM), epoxides (especially PAH ), ethyleneimine and its derivatives, chloroethylamine, etc.).
• indirect - inactive substances forming covalently bound DNA adducts only after enzymatic activation, which occurs with the formation of highly active electrophilic metabolites capable of interacting with nucleophilic groups of DNA ( PAHs and their derivatives).

• Chemical carcinogens
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  Aflatoxin B1 is the strongest hepatocarcinogen and deadly mycotoxin ^[17] .

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  Benzene is a strong carcinogen, has a pronounced myelotoxic effect (affects the bone marrow), thereby causing aplastic anemia , leukemia and other diseases of the hematopoietic system (hematopoiesis) ^{[18] [19]} .

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  Methyl cholanthrene is the strongest carcinogen, is formed in the human body, as a result of a violation of cholesterol metabolism. Causes adenocarcinoma of the prostate gland.

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  Ethylene oxide - has a strong alkylating effect on the nucleophilic groups of the DNA molecule, causing mutations.

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  Vinyl chloride is a toxic and carcinogenic substance. It affects the liver (causes angiosarcoma ), lungs, the central nervous system, the hematopoiesis system and the immune system.

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  Dimethylnitrosamine is one of the most common nitrosamines, highly toxic, causes stomach cancer , hepatocellular carcinoma and irreversible damage to the liver.

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  2,3,7,8-Tetrachlorodibenzodioxin or TCDD is one of the most extremely toxic compounds of anthropogenic origin, has strong carcinogenicity, mutagen , teratogen , reduces the activity of the hematopoietic, endocrine, reproductive system, immunosuppressor . Causes malignant neoplasms of the liver, blood and breast.

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  Ethanol or ethyl alcohol, in everyday life "alcohol" , exhibits carcinogenic and mutagenic properties, is a narcotic substance, inhibits the activity of the central nervous system. Chronic use of alcohol containing high concentrations of ethanol increases the risk of malignant diseases of the digestive tract, blood system, nervous system and brain.

The most well-known physical carcinogens are various types of ionizing radiation ( α , β , γ radiation, x-ray x radiation, neutron radiation , proton radiation , cluster radioactivity , ion fluxes, fission fragments ), although they are also used to treat cancer. Ultraviolet is completely absorbed by the skin, and therefore can only cause melanoma . Whereas ionizing radiation , freely penetrating into the body, can cause radiogenic tumors of any tissues and organs of the body (quite often hematopoietic, due to high sensitivity). Microwave radiation .

The role of biological factors in carcinogenesis is not as great as that of chemical and physical factors, but in the etiology of some malignant tumors, it is very significant. Thus, up to 25% of cases of primary liver cancer in the countries of Asia and Africa are associated with infection with the hepatitis B virus . About 300,000 cases of cervical cancer per year and a significant proportion of penile cancer cases are associated with sexually transmitted papillomaviruses (primarily HPV-16 , HPV-18 , HPV-33 ) ^[20] . Approximately 30–50% of Hodgkin’s lymphoma cases are associated with the Epstein — Barr virus damage to the human body ^[21] .

In the 1990s, convincing data were obtained on the dependence of most varieties of gastric cancer on infection by the bacterium Helicobacter pylori ^[2] .

• List of carcinogens from IARC. Category 1
• Chemical carcinogenesis
• Traffic fumes
• DNA adduct

• Cherenkov VG Clinical Oncology. 3rd ed. - M .: Medical book, 2010. - 434 p. - ISBN 978-5-91894-002-0 .

• GN 1.1.725-98 “List of substances, products, production processes, domestic and natural factors that are carcinogenic to humans” (invalidated since 28.06.2008)
• SanPiN 1.2.2353-08 “Carcinogenic factors and basic requirements for the prevention of carcinogenic hazards” (effective from 28.06.2008)