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Effects of a 6-Month Vitamin Intervention on DNA Damage in Heavy Smokers¹

Divisions of Epidemiology [J. S. J.], Biostatistics [M. D. B.], and Environmental Health Sciences [L. W. W., Q. W., T-L. Y., D. Y., R. M. S.], Joseph L. Mailman School of Public Health of Columbia University, New York, New York 10032; Our Lady of Mercy Medical Center, Bronx, New York 10466 [E. N., M. A.]; and Roche Vitamin Inc., Parsippany, New Jersey 07054 [V. N. S.]

Because their formation is associated with tumor development in specific tissues, DNA adducts have potential usefulness as intermediate end points in chemoprevention studies. To determine the efficacy of a combination of antioxidant vitamins (vitamins C and E and ß-carotene), a randomized clinical trial was conducted among heavy smokers using DNA damage as the end point. Immunological methods were used to measure polycyclic aromatic hydrocarbon-DNA adducts and oxidative DNA damage (8-oxo or hydroxydeoxyguanosine) in mononuclear and oral cells. A total of 121 subjects were randomized to the 6-month intervention and received either vitamins or placebo. Dropout rates were higher in the placebo than in the vitamin group; 65% of subjects in the vitamin group, but only 47% in the placebo group, provided specimens at 6 months. Plasma levels of all three antioxidants rose significantly in the vitamin group but not in the placebo group. All four measures of DNA damage decreased in both groups; the between-group differences were not statistically significant. These data do not provide clear evidence that antioxidant vitamin intake prevents DNA damage. However, the study demonstrates that DNA damage is a useful end point in chemoprevention trials.

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