[adimed]

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.