Mechanisms of Chemical Carcinogenesis

Abstract

It is generally accepted that exposure to noxious chemicals is the single most important contributor to the incidence of human cancer. Invariably, exposure to such chemicals is through complex mixtures where it is often masked by the myriad of other materials present. In the majority of instances, exposure is frequently repeated, often over a lifetime. The consequence of this exposure is an interaction of the chemical with key biological macromolecules, usually DNA, resulting in biochemical changes that are, for the most part, unnoticed. Yet, such exposure, especially when cumulative, ultimately leads to a profound change in the behaviour of cells via a series of subtle and insidious events. At the point at which these chemical/environment‐mediated events give rise to cellular changes that can be detected (often the appearance of a lump), the damage has been done and the cancer is established. Defining how exposure to chemicals can lead to these complex biological events and ultimately to the development of neoplasia has been extremely important in our understanding of the aetiology of human cancer. This knowledge has aided and guided our approach to assessing the risk to such chemicals and has offered insights into how cancer can be avoided and treated.

Influence of cell cycle on responses of MCF-7 cells to benzo[a]pyrene

“…This damage can be manifested in several forms, including single or double strand breaks, apurinic sites and covalent modification of the bases. Some chemical carcinogens such as benzo[a]pyrene (BaP), which is a representative of the class of polycyclic aromatic hydrocarbons (PAHs), are thought to cause cancer through covalent binding of their reactive metabolites to DNA, forming DNA adducts [ 1 - 3 ]. BaP-7,8-diol-9,10-epoxides (BPDE), the ultimate carcinogenic metabolites of BaP, react predominantly with the N 2 position of guanine residues and to a lesser extent with the N 6 position of adenine residues in DNA [ 4 ].…”

Chemical carcinogenesis: A brief review on mechanism & metabolism

“…This implies that removal of the promoting agent causes no further proliferation of the initiated cell population. 14 The promotion stage comprises of epigenetic processes accountable for the development of the malignant phenotype and tumor cells survival. 15 The following products such as phorbol esters, hormones, phenols and drugs are by themselves non-tumorigenic but intensifies the carcinogenicity of chemicals.…”

“…This is accredited to either agent mediated or spontaneous pertaining to irreversible and progressive changes. 14 In the step of progression, a neoplastic phenotype is attained due to genetic and epigenetic means. Here, the proliferation is a self-governing process in spite of the presence or absence of progression-related stimuli.…”

The Photochemical Degradation (PCD) of Nitrobenzene (NB) using UV Light and Fenton Reagent Under Various Conditions

“…The growth of textile (16), pharmaceutical, and garment industries are the highest among all the industries (1,17). Nitrobenzene (NB) is one of the frequently used chemical for aniline manufacturing, solvent in the manufacturing paints, shoe polishes, floor polishes, metal polishes, explosive, rubber making, textile, pesticide, cosmetic, and pharmaceutical purposes (such as acetaminophen) (8,(18)(19)(20)(21)(22)(23). NB is a highly toxic organic pollutant (24).…”

“…NB is a highly toxic organic pollutant (24). NBs and their derivatives cause several harmful health effects, for example, nitrobenzene can reduce the ability of blood to carry oxygen because it causes methemoglobinemia (8,19). Repeated exposure to high level of it may cause anemia, development of bluish colour in the skin, headache, nausea, weakness, sleepiness, vomiting, grouchiness, and dizziness (25).…”