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An Introduction on Chemical Carcinogens
#1
We are exposed to ‘n’ number of chemicals everyday in both indoor and outdoor environment. The essential household products we use like toothpaste, soap, shampoos, detergents, drugs/medicines, floor and toilet cleaners, insect repellents, food additives, paints are all chemicals. In the same way we are exposed to chemicals in the outdoor environment while travelling or in work places with or without our knowledge. Any product meant for human use is evaluated for its safety before reaching the market. Toxicology, a branch of science takes the predominant position in evaluating the adverse effects of pharmacological drugs and chemicals on animals or humans, their metabolic pathway once entering the biological system and the biotransformation of such chemicals inside the body. This gives complete knowledge on the toxic effects, details on dosage and length of exposure causing undesirable effect, the metabolic pathway and its target site/organ of the studied chemical which makes the process of identifying the effect and treating the exposed individual easier.

Based on the adverse effect developed by a chemical it is classified either as a toxicant or carcinogen. The difference is that the damage caused by the former category is reversible whereas the damage caused by the chemicals under the latter category “carcinogens” is irreversible. Carcinogens are the substances with the potential to cause cancer in the exposed individual or animal and there are many chemicals identified with carcinogenic property. The history of chemical carcinogenesis states the first identified chemicals to be carcinogens were soot, coal tar, aromatic amine and azo dyes.

The intensity of the effect of a chemical carcinogen on the host is governed by various factors. Those include,
• Dose of the chemical
• Length of exposure
• Metabolic pathway (from the point of entry to the target organ)
• Biotransformation (Resultant product after the metabolism of the chemical in the body which may be more toxic than the original compound)
• Species, age and gender of the subject
• Altered carcinogenicity of the chemical on interaction with other environmental factors

Classification
Chemical carcinogens are classified into Genotoxic and non Genotoxic compounds based on their potential to cause damage to the DNA of the exposed animal or man. Those chemical carcinogens which alter the genetic material of the exposed individual can also be called as mutagens.

Yet another classification of chemical carcinogens is made based on the requirement of metabolic activation of the chemical to deliver the effect. Accordingly they are classified as primary chemical carcinogens, secondary chemical carcinogens and promoters.

Primary chemical carcinogens are the chemicals whose effect is seen immediately at the point of entry itself even without undergoing metabolism. Alkylimine, triethylenemelamine, mustard gas are some of the examples.

Secondary chemical carcinogens are also called as procarcinogens are the chemicals whose effects are observed in the exposed individual due to the resultant product of metabolism of the compound in the system. Thee metabolically activated forms of Benzanthracene, aflatoxinB1, safrole, carbon tetrachloride are some of the procarcinogens.

Next class is the promoters which are also called as cocarcinogens are the chemicals which are not only carcinogenic but also acts as inducers stimulating the carcinogenic property of other chemicals.

Exposure to Chemical carcinogens
Indoor Exposure: Formaldehyde, perchloroethylene, paradichlorobenzene, cigarette smoke, trisodium nitrilotriacetate, asbestos are some of the compounds present in indoor environment in the form of various products or accessories are carcinogenic in nature.

Outdoor Exposure: Regular exposure to compounds like Arsenic, benzene, beryllium, cadmium, hexavalent chromium (VI), nickel, ethylene oxide in work places causes cancer. Persons who are at risk of such exposures in industries should follow the prescribed guidelines of occupational health and safety measures in order to avoid risking their health.

Apart from the above discussed chemical carcinogens the other two types of carcinogens are physical and biological carcinogens. Ultra violet rays is the best example of physical carcinogen, exposure to which causes skin cancer and viruses with the potential to alter the genetic material of the host cell causing cancer are biological carcinogens. Human Papilloma virus, Hepatitis B and C virus are examples of cancer causing viruses.

Not all toxicants are carcinogenic. The ability to cause irreversible damage, the additive effect at each exposure, the mechanism of action on the basic genetic material, increased potential in the presence of other substances all makes a carcinogen differ from a toxicant.
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#2
The knowledge about the association of chemicals to carcinogenesis has progressed radically ever since the early observations of Pott and Hill in the 1700’s. The observation by John Hill that people using snuff developed nasal cancer more commonly than the general population associated chemical exposure to the cancer development. On the other hand, chemical carcinogenesis can be dated back particularly to the observation done by Sir Percival Pott in the year 1775 describing the frequent occurrence of scrotum cancer in chimney sweepers in England. He stated that this was due to the significant exposure of the chimney sweepers to the soot.
A carcinogen is any agent that causes cancer. This may be because of the capability of the carcinogen to damage the genome or to disrupt the metabolic processes of the cell. Chemical carcinogenesis is considered to be a multi-stage process that initiates with the exposure of an individual to complex mixtures of chemicals. Carcinogens, when once internalized are normally subjected to competing metabolic pathways of activation and detoxication, even though some reactive environmental chemicals have the capability to act directly. The relative risk of an individual to carcinogenesis is governed by, difference between the individuals in the metabolism of carcinogens, along with differences in DNA-repair ability and response to tumor promoters.
The primary genetic change that occurs as the result of interaction of the carcinogen with DNA is called as tumor initiation. The initiated cells become altered irreversibly and are at higher risk of converting into malignant cells than the normal one. The clonal expansion of the initiated cell is facilitated by the epigenetic effects of tumour promoters. This selective, clonal magnification results in the development of a core of preneoplastic cells. These cells are more susceptible to progress toward tumorigenesis since they present a larger, more quickly proliferating target population for the further action of chemical carcinogens, oncogenic viruses, and various other cofactors. Additional genetic changes result in the accumulation of mutations, which may lead to the activation of proto-oncogenes and inactivation of tumor-suppressor genes, resulting in malignant conversion, tumor progression, and finally metastasis.
The understanding of elementary genetic mechanisms that regulate chemical carcinogenesis is increasing progressively, and its insights have aided the progress in methodologies that are designed to analyse human cancer risk and susceptibility factors.
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An Introduction on Chemical Carcinogens00