Nuclear DNA damages generated by reactive oxygen molecules (ROS) under oxidative stress and their relevance to human cancers, including ionizing radiation-induced neoplasia part I: Physical, chemical and molecular biology aspects

Oxidative stress (OS) occurs when the production of reactive oxygen species (ROS) overpowers the body’s natural defence, causing macromolecular damage. The role of OS in cancer initiation will depend on the likelihood of interaction between short lived ROS and nuclear DNA. For this reason, a description of the physico-chemical properties of the various ROS that have been suggested to be involved is included. DNA damages that are not repaired or mis-repaired during cell proliferation are necessary but not sufficient for cancer initiation. The characteristics of DNA pro-mutagenic lesions and their potential role in cancer induction will be assessed, while stressing quantitative aspects as well as the importance of DNA repair. A low level of a specific DNA adduct can be compensated for by its persistence and high pro-mutagenic potency. Because ionizing radiations generate some of the same oxidative ROS as those involved in OS, the cancer spectrum from whole body radiation exposure should be compared with that associated with OS. A causal link between electromagnetic radiations and human cancer lacks adequate scientific support. Current knowledge dictates that emphasis should be shifted from oxidative damages of low genotoxicity towards pro-mutagenic lesions induced by reaction products of nitrogen monoxide and complex highly reactive carbonyls, e.g. from the peroxidation of lipids. A common shortcoming when assessing the role of OS in disease is the failure to distinguish between cause and effect - i.e. could the indicators of harmful OS be the result of the pathological condition in question, rather than its cause? Further, little attention has been paid to exposure in food to some of the same ROS (e.g. reactive carbonyl compounds), as are generated endogenously by OS. Nor have the simultaneous presence of an ubiquitous high background of potent pro-carcinogenic DNA adducts which are not generated by ROS been taken into account.