A tobacco-specific carcinogen in the fetus

A tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (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 newborns whose mothers smoked during pregnancy. We set out to determine whether this carcinogen is present in the fetus in early pregnancy. Cell-free amniotic 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 confirmed by assays for cotinine plus N-beta-D-glucosiduronosyl-(S)-(-) cotinine 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 significant difference (p=0.0006). There was not convincing evidence of NNAL-Gluc in the AF. This study documents for the first time that the tobacco-specific carcinogen NNAL is present in the fetus in early pregnancy. Further rigorous epidemiological studies are needed to determine whether the offspring of smoking mothers have an increased lifetime risk of cancer.