Carcinogenic substances come from natural and man-made environment, and can induce human andAnimal cancerSubstances.According to its source, it can be divided into three categories: natural carcinogens, carcinogens generated in the process of raw material processing and synthetic carcinogens.
BiologicalCarcinogenic substances: there are biosynthetic products such as mycotoxins, alkaloids, glycosides, water and soil microorganisms, and low and high grade plants synthesize polycyclic aromatic compoundsHydrocarbon compound, animal and human hormones, etc;for examplehepatitis B virus、Herpes virusEtc.
Chinese name
Carcinogen
Foreign name
Carcinogen
Source
Substances that induce cancer in humans and animals
According to its source, it can be divided into three categories: natural carcinogens, carcinogens generated in the process of raw material processing and synthetic carcinogens.
According to its action mechanism, it can be divided into initiator (or initiator) and hair promoter.Both are calledComplete carcinogenOnly the initiator is called incomplete carcinogen.Some are neither initiators nor hair promoters, and they do not cause cancer, but can enhance the role of initiators and hair promoters, known as carcinogens.It can be divided into confirmed carcinogens, suspected carcinogens andPotential carcinogen。The mode of action can be divided into direct action and indirect action.There are more than 1100 known chemical carcinogens.according toworld health organizationAccording to the organization data, more than 140 animals have been identified as carcinogenicepidemiological investigation There are 21 confirmed to have carcinogenic effects on humans, and 18 suspected to have carcinogenic effects on humans.It is estimated that 80~85% of human cancers are related to chemical carcinogens.Recent research shows that many mutagens can cause cancer, and many carcinogens can also cause mutation. The two are closely related.
International classification
The International Cancer Research Institute under the World Health Organization divides carcinogens into four categories:
Class I: substances or mixtures with definite carcinogenicity to human body, such asAflatoxin、Arsenic, asbestosHexavalent chromium、dioxin, formaldehyde, alcoholRefined beverage, tobaccoBetel nutAnd processed meat (new in November 2015).
Class II A: substances or mixtures with high possibility of carcinogenesis to human body, and sufficient evidence of carcinogenicity has been found in animal experiments.Although it is theoretically carcinogenic to human body, the experimental evidence is limited.asAcrylamide、Inorganic lead compounds、chloramphenicolEtc.
Class II B: For substances or mixtures with low carcinogenicity to human beings, the evidence of carcinogenicity found in animal experiments is insufficient, and the evidence of carcinogenicity to human beings is limited.It is used to classify substances that are less likely to cause cancer than Category II A.such aschloroform、DDT, DDVPNaphthalene sanitary ball、Nickel metal、nitrobenzene、Diesel fuel, gasoline, etc.
Class III: substances or mixtures that have not been classified as carcinogenic to human beings, with insufficient evidence of carcinogenicity to human beings and insufficient or limited evidence of carcinogenicity to animals.Or there is sufficient experimental evidence and sufficient theoretical mechanism to show that it is carcinogenic to animals, but not to humans.asaniline 、Sudan red(After entering the human body, it can be metabolized as a Class II carcinogen, that is, a possible carcinogen for humans. Sudan red can also cause genetic mutation.[2]）、caffeine、xylene、saccharinAnd its salts, diazepamferric oxide、Organic lead compounds、Electrostatic magnetic field、melamine, mercury andinorganic compoundEtc.
Class IV: substances that may not be carcinogenic to human body and lack sufficient evidence to support their carcinogenicity.asCaprolactam。
IARC (2002) classifies 878 chemicals that have been reported into 4 categories according to their carcinogenic risks to humans.
Class 1: carcinogenic to humans, 87 kinds.The requirements for confirming human carcinogens are: ① epidemiological investigation with strict design, reliable method and ability to eliminate confounding factors; ②yesDose responseRelationship; ③There is also investigation data verification or animal experiment support.
Category 2A: 63 kinds are likely to cause cancer to people.This kind of carcinogen is harmful to human beingscarcinogenicityThe evidence is limited and sufficient for carcinogenicity of experimental animals.
Category 2B: 234 kinds that may cause cancer to humans.The evidence of carcinogenicity of such carcinogens to humans is limited, and the evidence of carcinogenicity to experimental animals is insufficient;Or there is insufficient evidence of carcinogenicity for humans and sufficient evidence of carcinogenicity for experimental animals.
Category 3: 493 types of carcinogenicity to human beings can not be classified, that is, suspected carcinogenicity to human beings;
Category 4: only one is likely not to cause cancer to humans.
According to the need of activation, carcinogens can be divided into: ① those that do not need activation are calledDirect carcinogen；②Those that need to be activated are called pre carcinogens orIndirect carcinogen。Its activitymetaboliteIt is the ultimate carcinogen.
According to whether it is mutagenic or carcinogenicSomatic mutationIt is established that carcinogens are divided into two categories: ① mutagenic carcinogens, also known as mutagenic carcinogensGenotoxic carcinogen；②Non mutagenic carcinogen, or non genotoxic carcinogen.It is also called DNA active orgeneExternal carcinogens.The so-called exogenous carcinogenesis of DNA activity does not include the mutagenic mechanism targeting DNA.It is known that most tumor cells have genetic changes, and sometimes it is difficult to distinguish these changes from the cause of cancer or the result of cancer.IARC (1983) has long pointed out that according to the carcinogenic mechanismChemical carcinogenThe classification cannot be exhaustive and accurate.
Some chemicals are not carcinogenic in themselves, but their application before or at the same time can significantly enhance the occurrence of cancer, which can promote the carcinogenic process. Such substances are called carcinogens.[1]
Carcinogen toxicity
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Genotoxicity
Most "classic" organic carcinogens basically belong to this category.
⑴ The inherent characteristic of the chemical structure of direct carcinogens is that they have electrophilic activity without metabolic activation (with few exceptions) and can covalently combine with nucleophilic molecules (including DNA) to form adducts.The vast majority of these substances are synthetic organics, including: lactones (such as β - propenyllactone, propane sulfonate lactone and a, β - unsaturated hexacyclic propyl ester);OlefinizationEpoxide(such as 1,2,3,4-butadiene epoxide);Sub gum;Sulfate ester；Mustard gas and nitrogen mustard, etc;Active halogenated hydrocarbons (such as dichloromethyl ether, benzyl chloride, methyl iodine anddimethylcarbamoyl chloride ）Among them, the carcinogenic activity of higher halogenated hydrocarbon homologues of dichloromethol decreases with the increase of carbon atoms of alkyl group.In addition to the aforementioned alkylating agents, some platinum coordination complexes (such as dichlorodiaminoplatinum, dichloro (pyrrolidine) platinum, and dioxy-1, 2-diamocyclohexane platinum) also have direct carcinogenic activity. Generally, the cis isomer is more active than the trans isomer.
⑵ Indirect carcinogens such carcinogens can not cause cancer locally but in the tissues where metabolic activation occurs.Pre carcinogens can be divided into natural and synthetic categories.Synthetic products include: polycyclic or heterocyclic aromatic hydrocarbons [such as benzo (a) pyrene, benzo (a) anthracene3-Methylcholanthrene7,12-H toluene (a) anthracene, dibenzo (a, h) anthracene, etc.];Monocyclic aromatic amine (such as o-toluidine, o-anisidine);Bicyclic or polycyclic aromatic amine (such as2-NaphthylamineBenzidine, etc.);Quinoline (such as benzo (g) quinoline, etc.);Nitrofuran；Azo compound(such as dimethylaminoazobenzene);Chain or cyclic nitrosamines almost all cause cancer.However, with the different alkyl groups, the target organs are different;Dimethylhydrazine in alkyl hydrazine can cause cancer, and hydrazine itself has weak carcinogenicity;Formaldehyde andacetaldehyde；CarbamateAcetic acid, propyl ester and butyl ester in class A are carcinogenic, among whichUrethane(Urethane, also known as urethane) has the strongest carcinogenic ability, and the hepatocarcinogenic effect of vinyl chloride in halogenated hydrocarbons has attracted extensive attention in recent years.It is characterized by inducingHepatic angiosarcoma。Natural substances and their processed products account for 5 of the 34 human carcinogens announced by the International Anti Cancer Alliance (IARC) in 1978, including aflatoxin, cyclosporine A, tobacco and smoke, betel nut and alcoholic beverages.
Aflatoxin B1It is one of the strongest carcinogens, and the carcinogenic capacity of aflatoxin G1 is much lower.AflatoxinB2 and G2 are not carcinogenic in themselves, but it is believed that B2 canBiotransformationA small part becomes B1, so it also has certain carcinogenic capacity.Aflatoxin B1 can induce liver cancer in humans and various experimental animals except mice, and can also induce renal cancer and colon cancer under special conditions.Mice are not susceptible to GSHTransferasesIt has a high level of vitality and can effectively detoxify.The products of some toxic bacteria, such as cyclosporine A, doxorubicin, daunomycin, and gentamicin, are also pre carcinogens.These substances are often used as medicines.Even if tobacco is not burned and pyrolyzed, it will contain carcinogens such as nitroso nornicotine.Tobacco smoke also contains a variety of carcinogens, such as polycyclic aromatic hydrocarbonsHeterocyclic compound、PhenolsCarcinogens such as derivatives.Tobacco smoke also contains a large amount ofCancer promoterThis is one of the reasons for promoting smoking cessation.Contains when chewing tobacco leaves and using snuffNitrosamineIt can induce oral cancer and upper respiratory tract cancer.Betel nutInArecolineIt can form nitrosamines. Chewing betel nut can increase the incidence and mortality of oral cancer and upper digestive tract cancer.
⑶ Inorganic carcinogens cobalt, radium and radon may cause cancer due to their radioactivity.Nickel, chromium, lead, beryllium and some of their salts can cause cancer under certain conditions, among which nickel and titanium are the most carcinogenic.
Non genotoxicity
Carcinogens that cannot react with DNA according to tests.
(1) Although cancer promoters alone do not cause cancer, they can promote carcinogens with sub carcinogenic dose to cause cancer after starting to contact with the body, so it is considered that cancer promotion is a necessary condition for carcinogenesis.TPA is a two-stage mouseSkin cancerTypical in induction testCancer promoterIt has cancer promoting effect in various cell systems in vitro.PhenobarbitalIt can promote the development of liver cancer in rats or mice.Tryptophan and its metabolites and saccharin also have cancer promoting effects on bladder cancer.In recent years, butylated hydroxytoluene (BHT) has been widely used as a tumor promoter to induce lung tumors in miceHepatocellular adenomaAnd bladder cancer.DDT、Polyhalogenated biphenylsChlordaneTCDD is a liver cancer promoter.It is worth noting that it may be due to the induction of metabolic enzymes, and the detoxification process, especially the enhanced binding reaction. When some cancer promoters are ingested at the same time with the promoter, they may reduce the occurrence of tumors, such as phenobarbital, DDT and BHT.But they were found to act as cancer promoters.
⑵ The oldest theory of cytotoxicity holds that chronic stimulation can cause cancer, and that substances that cause cell death can cause compensatory proliferation, leading to tumors.The exact mechanism is still unclear, but it may involve the increased susceptibility of the body to the carcinogenic effect of environmental harmful factors.Some chlorinated hydrocarbonsCancer promoterThe mechanism may be related to cytotoxicity.Azotriacetic acid(nitrotropic acid, NTA) can cause renal and bladder cancer in rats and mice. It is preliminarily found that its mechanism of action is to bring zinc in the blood into the renal tubular ultrafiltrate and be reabsorbed by the renal tubular epithelium.Because zinc is toxic to these cells, it can cause damage and lead to cell death, resulting in proliferation and renal tumor formation.In the urine, NTA also complexs with calcium, making calcium exudate from the transitional epithelium of the renal pelvis and bladder, thus stimulatingcell proliferationAnd form tumors.
⑶ It was found 40 years ago that estrogen can cause animal tumors.Later, it was found that most substances that interfere with the function of endocrine organs can increase the number of tumors in these organs.The carcinogenic mechanism of estrogen is still unclear, but it is likely to be related to its carcinogenic effect;It is generally believed that it is necessary to maintain high levels of hormones in the body for a long time to induce tumors in endocrine sensitive organs.When pregnant women use synthetic estrogen (diethylstilbestrol, DES) to protect the fetus, it may cause vagina in adolescent womenClear cell carcinoma。The mechanism is quite complicated.
⑷ImmunosuppressantThe immunosuppression process affects tumor formation in many ways.Azathioprine、6-mercaptopurineSuch immunosuppressants or immune sera can cause leukemia or lymphoma in animals and humans, but rarely solid tumors.Cyclosporine A is a neworgan transplantThe immunosuppressant used in was once considered not carcinogenic.However, it has been found that the incidence of lymphoma in patients who have used the drug has increased.
⑸ Solid substance rodents can cause sarcoma formation after a long incubation period after embedding plastic subcutaneously.Its chemical composition is not important. As long as it is thin, even metal and various plastics can also lead to tumor formation.The key is size and shape, and the smooth ones are more effective than the rough ones, while the ones with holes are less effective than those without holes.Its mechanism of action may be that solid substances canFibroblastProliferation provides the substrate.Asbestos and other mineral dusts, such as uranium ore or hematite dust, can enhance the effect of smoking on lung cancer.
(6) Peroxisome proliferators have various substances that can cause the proliferation of peroxisomes in rodent liver to induce liver tumors.The peroxisome proliferators that have been found include the lipid-lowering drug clofribate, fenofibrate, gemfiber, tibric acid, plasticizer di - (2-ethylhexyl) benzoate and organic solvent 1, l, 2-trichloroethylene.Antamine and bis (2-ethylbaryl)PhthalateIt has a promoting effect on liver tumors, but the carcinogenic mechanism of such substances cannot be summarized by its carcinogenic effect.liverPeroxisomesAnd H202 increase, which can lead to the increase of reactive oxygen species, signal transduction, DNA damage and start the carcinogenic process.
Undetermined toxicity
As mentioned earlier, some halogenated hydrocarbons are genotoxic carcinogens, and others are cancer promoters.Others, such as carbon tetrachloride, chloroform, and some polychlorides, have not yet been fully clarifiedalkaneAnd olefins, etc.These substancesMutagenicity testIn vivo and in vitro studies have not shown that it can be converted into active electrophilic metabolites.Thiourea, Thioacetamide, ThioureapyrimidineAnd similarThioamideClass A is carcinogenic.The target organ is the thyroid gland, sometimes the liver.Thiopyrine, an antihistamine, was once widely used as a hypnotic in the United States, and was later found to induce liver cancer in rats.In addition, some scholars and research institutions also divide carcinogens into confirmed carcinogens, suspected carcinogens and potential carcinogens.In addition, pressChemical structureClassification, such as alkylationPolycyclic aromatic hydrocarbonsClassNitrosamineClass A, phytotoxins, metals, etc.[1]
give an example
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In food
Nitroso compoundHigh fat substances, high concentration alcohol, etc.Among them, the precursor of nitroso compounds has a high content in stale food, such as decayed foodAtrophic gastritisOr when the secretion of gastric acid components is insufficient, the stomach combines the precursors of nitroso compounds into nitroso compounds.
Food contamination
Agricultural pesticides and household detergents may contain carcinogenic compounds, and the food in contact with them may be contaminated.
Some hormone preparations can be treated by veterinarians orfeed additive Enters into edible poultry and domestic animals, thus inducingendocrine systemRelated tumors.
someFood packaging materialsIt contains a variety of cycloaromatic hydrocarbon based substances and has potential carcinogenicity.asFood packaging bag, wrapping paper, etc.
Carcinogenic substances in the air accumulate in food through soil, water and other ways.
additive
Such as nitrosamines contained in preservatives, food pigments, spices, flavorings and other additives.
Food processing savings
Smoked food and pickled food contain a large amount of cycloaromatic hydrocarbon carcinogens, which are contained in moldy rice, corn and beansAflatoxinIt has a strong carcinogenic effect on humans and animals.
Medical researchers have found that more than 10 chemicals have carcinogenic effects, among which nitrosamines, benzopyrene and aflatoxin are generally recognizedThree major carcinogensThey are closely related to diet.
Nitrosamines
It can cause almost all organ tumors in the human body, of which digestive tract cancer is the most common.Nitrosamine compounds are commonly found in grains, milk, cheese, tobacco and wine, bacon, barbecue, sea fish, canned food and drinking water.Unfresh food (especially vegetables cooked for a long time)nitriteThe content of is high.
Benzopyrene
It is mainly produced in the combustion process of coal, oil, natural gas and other substances. Fat and cholesterol can also form benzopyrene under high temperature. The content of benzopyrene in smoked products such as sausage can be 60 times higher than that of common meat.Proven, long-term exposureBenzopyreneIn addition to lung cancer, it can also cause gastrointestinal cancer, bladder cancer, breast cancer, etc.
Aflatoxin
It is the strongest known carcinogen.Medical experts believe that aflatoxin may be an important cause of liver cancer.In some areas with high incidence of liver cancer, people often eat fermented foods such as fermented bean curd, bean paste, etc. Such foods are easy to produce aflatoxin if they are made improperly.
In order to prevent the above several major carcinogens from acting strangely and reduce and weaken the threat of carcinogens to human beings, people must adopt scientific methods in food production, processing and cooking.
Salted fish
Salted fish produce dimethyl nitrite, which can be transformed into the carcinogen dimethylnitrite in the body.If a person regularly eats salted fish from birth to the age of 10, he or she is 30-40 times more likely to suffer from nasopharyngeal cancer in the future than those who do not eat salted fish.Fish sauce, shrimp paste, salted eggs, pickles, sausages, ham, and smoked pork also contain more nitrite carcinogens, so you should try to eat less.
Barbecue food
Roast beef, roast duck, roast lamb, roast goose, roast pork, etc.Because it contains strong carcinogens3,4-BenzopyreneIt is not advisable to eat more.
smoked provisions
Such as smoked meat, smoked liver, smoked fish, smoked eggs, smoked dried bean curd, etc. also contain benzopyrene carcinogens, which can easily lead to esophageal cancer and gastric cancer.
fried food
The carcinogen polycyclic aromatic hydrocarbons (PAHs) will be produced after frying too much coke.After roasted coffee beans, the content of benzopyrene increased 20 times.Oil pancakes, stinky tofu, fried taro, fried dough sticks, etc., most of which are used repeatedly, will produce a carcinogenic decomposition product under high temperature.
Moldy food
Rice, wheat, beans, corn, peanuts and other foods are susceptible to moisture and mildew, and various carcinogenic toxins will be produced after being contaminated by mold.
Overnight cooked cabbage
It will produce nitrite, which will be transformed into nitrite amine carcinogen in the body.
Betel nut
Chewing betel nut is a factor that causes oral cancer.
Undrinkable water and ditch water
Gastric cancer, esophageal cancer and liver cancer are all related to drinking pond water.People who regularly drink unburned tap water will be 21% more likely to suffer from bladder cancer and 38% more likely to suffer from rectal cancer.[1]
