Abstract
Oxidative DNA damage can result from numerous endogenous metabolic processes as well as from exposure to environmental and dietary oxidants. One important type of oxidative DNA damage is the formation of hydroxylated DNA bases. This type of DNA damage may have a role in carcinogenesis. We examined the levels of a hydroxylated thymine residue, 5-hydroxy-methyl-2'-deoxyuridine, in DNA obtained from the peripheral blood of breast cancer patients and control women. The isolated DNA was analyzed for levels of 5-hydroxymethyl-2'-deoxyuridine by gas chromatography with mass spectral detection. The levels of this modified base were significantly higher in 25 breast cancer patients compared with 38 controls, with levels of 0.112 +/- 0.046 in the cancer patients versus 0.083 - 0.025 in the controls, given as pg 5-hydroxymethyl-2'-deoxyuridine/ng thymidine, mean +/- standard deviation (P = 0.019). After controlling for various covariates, the adjusted mean levels of oxidative DNA damage were still significantly higher in women with breast cancer relative to controls. These results indicate that the levels of 5-hydroxymethyl-2'-deoxyuridine in DNA from peripheral nucleated blood may be potentially useful as a marker of breast cancer.
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