Carcinogen

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Carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis, cancer formation. This may be due to the ability to damage the genome or the disruption of cellular metabolic processes. Some radioactive substances are considered carcinogens, but their carcinogenic activity is associated with radiation, such as gamma rays and alpha particles, which it emits. Common examples of non-radioactive carcinogens are inhaled asbestos, certain dioxins, and tobacco smoke. Although society generally associates carcinogenicity with synthetic chemicals, it is equally likely to arise in both natural and synthetic substances. Carcinogens are not always toxic; thus, the effect may be harmful.

Cancer is a disease in which normal cells are damaged and do not undergo programmed cell death as soon as they divide through mitosis. Carcinogens can increase the risk of cancer by altering cell metabolism or destroying DNA directly inside cells, which interfere with biological processes, and induce uncontrolled malignant divisions, leading eventually to tumor formation. Usually, severe DNA damage leads to programmed cell death, but if the programmed cell death path is damaged, then the cell can not prevent itself into cancer cells.

There are many natural carcinogens. Aflatoxin B ₁ , produced by the Aspergillus flavus fungus that grows on stored grains, beans and peanut butter, is an example of a potent and naturally occurring microbial carcinogen. Certain viruses such as hepatitis B and human papilloma virus have been found to cause cancer in humans. The first proven cause of cancer in animals is the Rous's sarcoma virus, discovered in 1910 by Peyton Rous. Other infectious organisms that cause cancer in humans include some bacteria (eg Helicobacter pylori ) and worms (eg Opisthorchis viverrini and Clonorchis sinensis .

Dioxins and dioxins, benzene, kepone, EDB, and asbestos are all classified as carcinogenic. As far back as the 1930s, industrial smoke and tobacco smoke were identified as the source of dozens of carcinogens, including benzo [pyrene], nitrosamine specific tobacco such as nitrosonornicotine, and reactive aldehyde such as formaldehyde, which is also harmful in embalming and making Plastic. Vinyl chloride, from which PVC is produced, is a carcinogen and thus is harmful in PVC production.

Co-carcinogens are chemicals that do not always cause cancer alone, but promote the activity of other carcinogens in causing cancer.

Once the carcinogen enters the body, the body attempts to eliminate it through a process called biotransformation. The purpose of this reaction is to make the carcinogen more soluble in water so it can be removed from the body. However, in some cases, this reaction can also convert less toxic carcinogens into more toxic carcinogens.

DNA is nucleophilic; therefore, dissolved carbon electrophiles are carcinogenic, since DNA attacks them. For example, some alkenes are poisoned by human enzymes to produce electrophilic epoxides. DNA attacks the epoxide, and is permanently bonded to it. This is the mechanism behind the carcinogenicity benzo [ a ] pyrene in tobacco, other aromatic fumes, aflatoxin and mustard gas.

Video Carcinogen

Radiation

CERCLA identifies all radionuclides as carcinogens, despite the radiated nature of radiation (alpha, beta, gamma, or neutron and radioactive strength), its consequent capacity to cause ionisation in the tissues, and the magnitude of radiation exposure, determines potential hazards. Radiation carcinogenicity depends on the type of radiation, type of exposure, and penetration. For example, alpha radiation has low penetration and is not a danger outside the body, but emitters are carcinogenic when inhaled or swallowed. For example, Thorotrast, a suspension (radioactive) previously used as a contrast medium in x-ray diagnostics, is a potent human carcinogen known for its retention in various organs and continuous emission of alpha particles. Low-level ionizing radiation can cause irreversible DNA damage (causing the replicative and transcriptional errors necessary for neoplasia or may trigger viral interactions) leading to premature aging and cancer.

Not all types of electromagnetic radiation are carcinogenic. Low-energy waves in the electromagnetic spectrum including radio waves, microwaves, infrared radiation and visible light are not considered, as they do not have enough energy to break chemical bonds. The evidence for the carcinogenic effect of non-ionizing radiation is generally unconvincing, although there are several cases of radar technicians documented with prolonged exposure experienced a significantly higher incidence of cancer.

High-energy radiation, including ultraviolet radiation (present in the sun), x-rays, and gamma radiation, is generally , if received in sufficient doses. For most people, ultraviolet radiation 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 commonly diagnosed cancer in people aged 15-44.

Substances or foods irradiated with electrons or electromagnetic radiation (such as microwaves, X-rays or gamma) are not carcinogenic. In contrast, non-electromagnetic neutron radiation generated inside a nuclear reactor can produce secondary radiation through nuclear transmutation.

Maps Carcinogen

In ready-to-eat foods

Chemicals used in processed and preserved meats such as some brands of bacon, sausage and ham may or may not produce carcinogens. For example, the nitrite used as a preservative in preserved meat such as bacon has also been recorded as carcinogenic with demographic links, but not a cause, for colon cancer. Cooking foods at high temperatures, such as roasting or roasting meat, can, or can not, also lead to the formation of a small number of potential carcinogens comparable to those found in cigarette smoke (ie, benzo [ a ] pyrene). Charring foods look like coke and pyrolysis tobacco, and produce 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-cook the meat in the microwave oven for 2-3 minutes before baking shorter time on the hot pot, and remove the heterocyclic amine precursor (HCA), which can help minimize the formation of this carcinogen.

Reports from the Food Standards Agency have found that acarslamide animal carcinogens are known to be produced in fried or overheated carbohydrate foods (such as potato fries and potato chips). Studies are underway at the FDA and European regulatory agencies to assess the potential risks to humans.

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In cigarettes

There is a strong smoking association with lung cancer; lifetime risk of developing lung cancer increased significantly in smokers. A large number of known carcinogens are found in cigarette smoke. Potential carcinogens found in cigarette smoke include aromatic polycyclic hydrocarbons (PAHs, such as benzo [a] pyrene), Benzene, and Nitrosamine.

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Mechanism of carcinogenicity

Carcinogens can be classified as either genotoxic or nongenotoxic. Genotoxins cause irreversible damage or genetic mutations by binding to DNA. Genotoxins include chemical agents such as 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.

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Classification

International Agency for Research on Cancer

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

• Group 1: the agent (mixture) is definitely carcinogenic in humans. The state of illumination involves a carcinogenic exposure in humans.
• Group 2A: the agent (mixture) may be carcinogenic in humans. The state of lighting involves exposures that may be carcinogenic in humans.
• Group 2B: the (mixed) agent may be carcinogenic in humans. The state of lighting involves exposures that may be carcinogenic to humans.
• Group 3: the agent (mixed state or exposure) can not be classified as the cause of its carcinogenesis in humans.
• Group 4: agents (mixtures) may not be carcinogenic in humans.

Global Harmonization System

The globally harmonized Global Classification and Supply System (GHS) is a United Nations initiative to attempt to harmonize different systems in assessing current chemical risk (as of March 2009) worldwide. It classifies carcinogens into two categories, the former being subdivided into subcategories if desired by a competent regulatory authority:

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

AS. National Toxicology Program

The National Toxicology Program of the US Department of Health and Human Services is mandated to produce a biennial report on the Carcinogen Report. Until June 2011, the latest edition is the 12th report (2011). It classifies carcinogens into two groups:

• Known as a human carcinogen
• Quite anticipated to be a human carcinogen

America's American Conference Conference on Industrial Hygiene

The American Government Hygiene Industrial Experts Conference (ACGIH) is the best known private organization for the publication of the TLV for exposure and workplace chemistry monographic workplace hazards. This assesses carcinogenicity as part of a broader assessment of the dangers of chemical work.

• Group A1: A confirmed human carcinogen
• Group A2: Suspected human carcinogen
• Group A3: Confirmed animal carcinogens with unknown relevance to humans
• Group A4: Can not be classified as a human carcinogen
• Group A5: Not suspected as a human carcinogen

European Union

The classification of EU carcinogens is contained in the Harmful Instructions and Guidelines of Dangerous Preparation. It consists of three categories:

• Category 1: Substances known to be carcinogenic in humans.
• Category 2: Substances that should be regarded as carcinogenic in humans.
• Category 3: Substances causing concern for humans, because of possible carcinogenic effects, but in this respect the available information is insufficient to make satisfactory judgments.

This scoring scheme is being removed for the GHS scheme (see above), which is very close to the definition of the category.

Australian Safe Work

Under the previous name, NOHSC, in 1999 Safe Work Australia issued Approved Criteria for Classifying Hazardous Substances [NOHSC: 1008 (1999)]. 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 in humans.
• Category 2: Substances that should be regarded as carcinogenic in humans.
• Category 3: Substances that have a carcinogenic effect on humans but lack information to make judgments.

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Procarcinogen

Procarsinogen is a precursor for carcinogens. One example is nitrite when taken by diet. They are not carcinogenic, but turn into nitrosamines in the body, which can be carcinogenic.

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Common carcinogens

Work carcinogen

Occupational carcinogens are agents that pose a cancer risk in some specific work sites:

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• Gasoline (contains aromatics)
• Lead and its compounds
• Alkylating antineoplastic agents (eg mechlorethamine)
• Other alkylation agents (eg dimethyl sulphate)
• Ultraviolet radiation from the sun and UV lights
• Alcohol (causes head and neck cancer)
• Other ionizing radiation (X-rays, gamma rays, etc.)

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The primary carcinogen is involved in four most common cancers worldwide

In this section, carcinogens involved as the main causative agent 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 cancer incidence worldwide and 42% cancer deaths (for more details on carcinogens involved in this and other cancers, see references).

Lung cancer

Pulmonary cancer (pulmonary carcinoma) is the most common cancer in the world, both in cases (1.6 million cases, 12.7% of total cases of cancer) and death (1.4 million deaths, 18.2% of total death from cancer). Lung cancer is mostly caused by tobacco smoke. Estimated risk for lung cancer in the United States shows that cigarette smoke is responsible for 90% of lung cancers. Other factors are involved in lung cancer, and these factors can interact synergistically with smoking so that the 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%). Tobacco smoke is a complex mix of more than 5,300 chemicals identified. The most important carcinogen in tobacco smoke has been determined by the Margin of Exposure approach. Using this approach, the most important tumorigenic compounds in tobacco smoke, 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 changes in DNA. DNA damage is subject to an error-prone DNA repair or may lead to replication errors. Such errors in repair or replication may result in mutations in tumor suppressor genes or oncogenes that cause cancer.

Breast cancer

Breast cancer is the second most common cancer [(1.4 million cases, 10.9%), but the 5th rank as the cause of death (458,000, 6.1%)]. Increased risk of breast cancer is associated with elevated levels of estrogen in the blood. Estrogen appears to contribute to breast carcinogenesis by three processes; (1) estrogen metabolism for genotoxic, mutagenic carcinogens, (2) stimulation of tissue growth, and (3) repression of phase II detoxification enzymes that metabolize ROS leading to increased oxidative DNA damage. The main estrogen in humans, estradiol, can be metabolized into quinone derivatives that form adducts with DNA. These derivatives can lead to duplication, base removal of the DNA phosphodiester backbone, followed by an inaccurate repair or replication of the apical site that causes mutations and ultimately cancer. This genotoxic mechanism can interact synergistically with estrogen-mediated, persistent cell proliferation to ultimately lead to breast cancer. Genetic background, dietary practices and environmental factors are also likely to 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%)]. Tobacco smoke can cause up to 20% of colorectal cancers in the United States. In addition, substantial evidence has implications for bile acids as an important factor in colon cancer. Twelve studies (summarized in Bernstein et al.) Show that bile acid deoxicidic acid (DCA) and/or lithocholic acid (LCA) induce production of reactive oxygen species that damage DNA and/or reactive nitrogen species in human or animal colon cells. Furthermore, 14 studies show that DCA and LCA induce DNA damage to colon cells. Also 27 studies reported that bile acids cause programmed cell death (apoptosis). Increased apoptosis may produce cell survival cells that are resistant to apoptotic induction. Colon cells with reduced ability to undergo apoptosis in response to DNA damage will tend to accumulate mutations, and such cells can cause colon cancer. Epidemiological studies have found that the concentration of stool bile acid increased in the population with high incidence of colon cancer. Increased total fat or saturated fatty diet results in increased DCA and LCA in feces and increased exposure of the colonic epithelium to bile acids. When DCA bile acids were added to the standard diet of invasive wild rats colon cancer induced in 56% of mice after 8 to 10 months. Overall, available evidence suggests that DCA and LCA are carcinogens that damage DNA that is central to colon cancer.

Stomach Cancer

Gastric cancer is the fourth most common cancer [990,000 cases (7.8%), 738,000 deaths (9.7%)]. Helicobacter pylori infection is a major contributing factor in stomach cancer. Chronic gastritis (inflammation) caused by H. pylori often lasts long if left untreated. Gastric epithelial infections with H. pylori result in increased production of reactive oxygen species (ROS). ROS causes oxidative DNA damage including major baseline changes of 8-hydroxydeoxyguanosine (8-OHdG). 8-OHdG resulting from ROS increases in chronic gastritis. Changed DNA bases can cause errors during replication of DNA that has mutagenic and carcinogenic potential. Thus H. pylori -induced ROS appears to be a major carcinogen in stomach cancer because they cause damage to oxidative DNA that causes carcinogenic mutations. Diet is considered a contributing factor in stomach cancer - in Japan where very salty pickled food is very popular, high incidence of stomach cancer. Preserved meats such as meat, sausages and hams increase the risk while a diet high in fresh fruits and vegetables can reduce the risk. Risk also increases with age.

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See also

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References

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External links

• US. National Toxicology Program Report on Carcinogens
• CDC - Occupational Cancer - List of Carcinogens - NIOSH Security and Health Topics
• Recognized Carcinogens
• American Cancer Society
• Carcinogen Rodent Database
• Compare the Likelihood of Cancer Dangers from Human Exposure to Rodent Carcinogens

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