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P.1476 right column 2nd paragraph: "DNA integrity is threatened from three sides. First, spontaneous reactions (mostly hydrolysis) intrinsic to the chemical nature of DNA in an aqueous solution create abasic sites and cause deamination [refs 12,13]. Second, our own metabolism generates reactive oxygen and nitrogen species, lipid peroxidation products, endogenous alkylating agents, estrogen and cholesterol metabolites, and reactive carbonyl species [ref 14], all of which damage DNA. Reactive oxygen and nitrogen species alone generate several kinds of single-strand breaks and more than 70 oxidative base and sugar products in DNA [ref 13]. Third, DNA is damaged by exogenous physical and chemical agents, but this damage is to some extent avoidable. The estimated numbers of single-strand breaks and spontaneous base losses in nuclear DNA are as high as 10^4 per cell per day [BNID 112970]. Together with other types of spontaneous damage, the total may be close to 10^5 lesions per cell per day [BNID 112970]. A single day in the sun can induce up to 10^5 UV photoproducts in each exposed keratinocyte, and inflammation can cause high levels of oxidative damage locally." |