Effects of a 6-month vitamin intervention on DNA damage in heavy smokers.
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 beta-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.
Jacobson
J S
JS
Division of Epidemiology, Joseph L. Mailman School of Public Health of Columbia University, New York, New York 10032, USA.
Begg
M D
MD
Wang
L W
LW
Wang
Q
Q
Agarwal
M
M
Norkus
E
E
Singh
V N
VN
Young
T L
TL
Yang
D
D
Santella
R M
RM
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D001205:Ascorbic Acid / Q000627:therapeutic use*; D018736:DNA Adducts / Q000032:analysis; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005982:Glutathione Transferase / Q000032:analysis; D006801:Humans; D016014:Linear Models; D008297:Male; D016017:Odds Ratio; D012907:Smoking / Q000009:adverse effects*; D014810:Vitamin E / Q000627:therapeutic use*; D019207:beta Carotene / Q000627:therapeutic use*
D018736:DNA Adducts; D019207:beta Carotene; D014810:Vitamin E; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005982:Glutathione Transferase; D003849:Deoxyguanosine; D001205:Ascorbic Acid