Chronic weight cycling increases oxidative DNA damage levels in mammary gland of female rats fed a high‐fat diet

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Abstract
Oxidative DNA damage levels may be a marker of breast cancer risk that is modulated by diet. We examined the effects of a high‐fat diet fed in varying feeding regimens on levels of 5‐hydroxymethyl‐2'‐deoxyuridine (5‐OHmU), an oxidized thymidine residue, in DNA from mammary gland of aging female rats. A total of 48 rats were randomly divided into four groups: ad libitum fed (AL), weight cycled above baseline (WC‐G), weight cycled below baseline (WC‐L), or energy restricted (ER) for 28 weeks. WC groups were fed repeated ad libitum/restricted amounts of the diet. At sacrifice, both WC groups had body weights similar to the ER group but higher levels of 5‐OHmU (p < 0.01). 5‐OHmU levels were higher in the WC groups than in the AL group, even though body weights of the WC groups were significantly lower (p < 0.001). These results indicate that a history of weight cycling, even when body weight is reduced, can have adverse effects on 5‐OHmU levels in mammary gland DNA, a potential biomarker of cancer risk. Constant control of calories for the maintenance of body weight, therefore, may be more beneficial.