Nida Rehmani and SM Hadi
One of the most intriguing scientific mysteries is the origin of cancer. DNA damage plays a potent role in mutagenesis, carcinogenesis and ageing. There has been growing realization in recent years that endogenous substrates or metabolites may be an important source of damage caused to cellular DNA. Further, evidence indicates that endogenous DNA damage occurs at a high frequency as compared to exogenous damage. Such findings have debunked the notion that the genetic material is pristine in the absence of exogenous carcinogens. An in-depth knowledge of the types of endogenous DNA damage is essential for understanding the influence of damage caused by endogenous substrates on the induction of cancer. Therefore, in this review, we have focused on several classes of endogenous metabolites and their putative role in mutagenesis and carcinogenesis from a structural, biological and analytical perspective. The mechanisms by which endogenous substrates may contribute to cancer pathogenesis have also been discussed with the objective that the implications from the findings summarised may pave way for a better understanding of the mechanisms underlying the induction of disease such as cancer. These results, complemented by other data, strongly support one of the theories of carcinogenesis according to which endogenous agents may have a major contribution in spontaneously induced cancer. It is obvious that if an approach could be developed leading to a diminution in endogenous DNA damage, the incidence of diseases such as cancer might be significantly reduced.
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