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The development of cancer in humans and animals is a multistep process. The complex series of cellular and molecular changes participating in cancer development are mediated by a diversity of endogenous and exogenous stimuli. One type of endogenous damage is that arising from intermediates of oxygen (dioxygen) reduction - oxygen-free radicals (OFR), which attacks not only the bases but also the deoxyribosyl backbone of DNA. Thanks to improvements in analytical techniques, a major achievement in the understanding of carcinogenesis in the past two decades has been the identification and quantification of various adducts of OFR with DNA. OFR are also known to attack other cellular components such as lipids, leaving behind reactive species that in turn can couple to DNA bases. Endogenous DNA lesions are genotoxic and induce mutations. The most extensively studied lesion is the formation of 8-OH-dG. This lesion is important because it is relatively easily formed and is mutagenic and therefore is a potential biomarker of carcinogenesis. Mutations that may arise from formation of 8-OH-dG involve GC --> TA transversions. In view of these findings, OFR are considered as an important class of carcinogens. The effect of OFR is balanced by the antioxidant action of non-enzymatic antioxidants as well as antioxidant enzymes. Non-enzymatic antioxidants involve vitamin C, vitamin E, carotenoids (CAR), selenium and others. However, under certain conditions, some antioxidants can also exhibit a pro-oxidant mechanism of action. For example, beta-carotene at high concentration and with increased partial pressure of dioxygen is known to behave as a pro-oxidant. Some concerns have also been raised over the potentially deleterious transition metal ion-mediated (iron, copper) pro-oxidant effect of vitamin C. Clinical studies mapping the effect of preventive antioxidants have shown surprisingly little or no effect on cancer incidence. The epidemiological trials together with in vitro experiments suggest that the optimal approach is to reduce endogenous and exogenous sources of oxidative stress, rather than increase intake of anti-oxidants. In this review, we highlight some major achievements in the study of DNA damage caused by OFR and the role in carcinogenesis played by oxidatively damaged DNA. The protective effect of antioxidants against free radicals is also discussed.

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Spectroscopic studies have been performed to investigate the high-affinity binding site for copper in human serum albumin (HSA) and dog serum albumin (DSA). A new approach based on exposure to albumin of the copper in the form of a well-characterized histidine (his) chelate has been adopted. This technique has been shown to minimize interaction at the lower affinity sites. The analysis of the S-band EPR spectrum of [Cu(his)2] at pH 7.3 revealed the major component is a complex formed with two histidines in a histamine-like coordination. Detailed analysis of S-band and X-band EPR and optical spectra of [Cu(II)−HSA] revealed that copper forms a complex with HSA involving α-NH2 terminal, two deprotonated peptide nitrogens (NH of Ala2, and NH of His3), and the imidazole nitrogen of His3 in a square planar arrangement. The spectral data were found to be independent of pH in the range 4.5−9.0 and did not confirm axial Asp1 carboxylate chelation. The EPR study of [Cu(II)−DSA] complex at pH 7.3 confirmed the presence of two bonded nitrogens which substantiate the absence of strategically located His3. It has been suggested that residues of non-nitrogen origin localized in the main body of DSA may be involved in copper binding, which would explain the protection from the Sanger reaction.