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Clear Differences in Levels of a Formaldehyde-DNA Adduct in Leukocytes of Smokers and Nonsmokers

Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota

Requests for reprints: Stephen S. Hecht, Masonic Cancer Center, University of Minnesota, MMC 806, 420 Delaware Street Southeast, Minneapolis, MN 55455. Phone: 612-624-7604; Fax: 612-626-5135; E-mail: hecht002{at}umn.edu.

Key Words: formaldehyde

Formaldehyde is considered carcinogenic to humans by the IARC, but there are no previous reports of formaldehyde-DNA adducts in humans. In this study, we used liquid chromatography-electrospray ionization-tandem mass spectrometry to quantify the formaldehyde-DNA adduct N⁶-hydroxymethyldeoxyadenosine (N⁶-HOMe-dAdo) in leukocyte DNA samples from 32 smokers of 10 cigarettes per day and 30 nonsmokers. Clear peaks coeluting with the internal standard in two different systems were seen in samples from smokers but rarely in nonsmokers. N⁶-HOMe-dAdo was detected in 29 of 32 smoker samples (mean ± SD, 179 ± 205 fmol/µmol dAdo). In contrast, it was detected in only 7 of 30 nonsmoker samples (15.5 ± 33.8 fmol/µmol dAdo; P < 0.001). The results of this study show remarkable differences between smokers and nonsmokers in levels of a leukocyte formaldehyde-DNA adduct, suggesting a potentially important and previously unrecognized role for formaldehyde as a cause of cancer induced by cigarette smoking. [Cancer Res 2009;69(18):7170–4]