Abstract
A large number of chemicals and several physical agents, such as UV light and γ-radiation, have been associated with the etiology of human cancer. Generation of DNA damage (also known as DNA adducts or lesions) induced by these agents is an important first step in the process of carcinogenesis. Evolutionary processes gave rise to DNA repair tools that are efficient in repairing damaged DNA; yet replication of damaged DNA may take place prior to repair, particularly when they are induced at a high frequency. Damaged DNA replication may lead to gene mutations, which in turn may give rise to altered proteins. Mutations in an oncogene, a tumor-suppressor gene, or a gene that controls the cell cycle can generate a clonal cell population with a distinct advantage in proliferation. Many such events, broadly divided into the stages of initiation, promotion, and progression, which may occur over a long period of time and transpire in the context of chronic exposure to carcinogens, can lead to the induction of human cancer. This is exemplified in the long-term use of tobacco being responsible for an increased risk of lung cancer. This mini-review attempts to summarize this wide area that centers on DNA damage as it relates to the development of human cancer.
Highlights
In 1761, after use of tobacco for recreation became popular in London, physician John Hill wrote a book entitled “Cautions Against the Immoderate Use of Snuff”
The mechanism of the in vivo effects of these carcinogens was little understood until DNA was shown to be the genetic material responsible for coding for all biological processes [21], and the structure of DNA was elucidated by Watson and Crick [22] on the basis of Rosalind Franklin’s unpublished crystal structure of DNA
It became gradually clear that many of the carcinogenic chemicals are metabolically activated to electrophilic species that bind to DNA or cause DNA damage [23,24,25]
Summary
In 1761, after use of tobacco for recreation became popular in London, physician John Hill wrote a book entitled “Cautions Against the Immoderate Use of Snuff”. A few years after Hill’s book was available, in 1775, Sir Percivall Pott of Saint Bartholomew’s Hospital in London published a groundbreaking essay showing that exposure to soot leads to high incidence of scrotal cancer in young men worked as chimney sweeps, which he named the chimney-sweepers’ cancer [1]. This was the first occupational link to cancer. Physical agents like UV light [17] and gamma radiation [18,19] turned out to be carcinogenic
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