A tobacco-specific carcinogen in the fetus

A tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butano l (NNAL), and its metabolite, 4-[(methylnitrosamino)-1-(3-pyridyl)but-1-yl] beta-O-D-glucosiduronic acid (NNAL-Gluc), have been found in the urine of n ewborns whose mothers smoked during pregnancy. We set out to determine whet her this carcinogen is present in the fetus in early pregnancy. Cell-free a mniotic fluid (AF) was obtained through routine amniocentesis for prenatal genetic studies from groups of smokers and non-smokers. NNAL and NNAL-Gluc were quantified by previously published methods. A history of smoking was c onfirmed by assays for cotinine plus N-beta-D-glucosiduronosyl-(S)-(-) coti nine inner salt (cotinine-Gluc) in AF. NNAL was detected in the AF of 11/21 (52.4%) of smokers and in 2/30 (6.7%) of non-smokers, a statistically sign ificant difference (p=0.0006). There was not convincing evidence of NNAL-Gl uc in the AF. This study documents for the first time that the tobacco-spec ific carcinogen NNAL is present in the fetus in early pregnancy. Further ri gorous epidemiological studies are needed to determine whether the offsprin g of smoking mothers have an increased lifetime risk of cancer. Copyright ( C) 2000 John Wiley & Sons, Ltd.