There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
A major development of carcinogenesis research in the past 20 years has been the discovery
of significant levels of DNA damage arising from endogenous cellular sources. Dramatic
improvements in analytical chemistry have provided sensitive and specific methodology
for identification and quantitation of DNA adducts. Application of these techniques
to the analysis of nuclear DNA from human tissues has debunked the notion that the
human genome is pristine in the absence of exposure to environmental carcinogens.
Much endogenous DNA damage arises from intermediates of oxygen reduction that either
attack the bases or the deoxyribosyl backbone of DNA. Alternatively, oxygen radicals
can attack other cellular components such as lipids to generate reactive intermediates
that couple to DNA bases. Endogenous DNA lesions are genotoxic and induce mutations
that are commonly observed in mutated oncogenes and tumor suppressor genes. Their
mutagenicity is mitigated by repair via base excision and nucleotide excision pathways.
The levels of oxidative DNA damage reported in many human tissues or in animal models
of carcinogenesis exceed the levels of lesions induced by exposure to exogenous carcinogenic
compounds. Thus, it seems likely that oxidative DNA damage is important in the etiology
of many human cancers. This review highlights some of the major accomplishments in
the study of oxidative DNA damage and its role in carcinogenesis. It also identifies
controversies that need to be resolved. Unraveling the contributions to tumorigenesis
of DNA damage from endogenous and exogenous sources represents a major challenge for
the future.