4-Aminobipheny1 Hemoglobin Adducts in Fetuses Exposed to the Tobacco Smoke Carcinogen In Utero

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Abstract
Maternal-fetal exchange of a potent tobacco-related human carcinogen, 4-aminobiphenyl, was studied in smoking(n=14) and nonsmoking (n=38) pregnant women. N-Hydroxy-4-aminobiphenyl, the active metabolite of 4-aminobiphenyl, forms chemical addition products (adducts) with hemoglobin. Levels of 4-aminobiphenyl hemoglobin adducts were measured in maternal-fetal paired blood samples obtained from smoking and nonsmoking women during labor and delivery. Carcinogen-hemoglobin adducts were detected in all maternal and fetal blood samples.Levels of such adducts were significantly higher (P<.001) in maternal and fetal blood samples from smokers: the mean 4-aminobiphenyl hemoglobin adduct level was 92+54 pg/g of hemoglobin in blood samples from fetuses of smokers, and 17+13 pg/g of hemoglobin in blood samples from fetuses of nonsmokers; the mean maternal 4-aminobiephenyl hemoglobin adduct level was 183 108 pg/g of hemoglobin in smokers, and 22 pg/g of hemoglobin in nonsmokers. Fetal Carcinogen-adduct levels were consistently lower than maternal levels: the mean maternal to fetal ratio was 2.4 1.1 in smokers and 1.9 98in nonsmokers. Fetal 4-aminobiphenyl hemoglobin adduct levels were strongly associated(correlation coefficient(r2)=.51, P=.002) with maternal 4-aminobiphenyl hemoglobin adduct levels when paired samples from smoking mothers were analyzed. A measure of third trimester to bacco smoke exposure based on number of cigarettes smoked per day, amount of each cigarette smoked, and depth of inhalation was associated (r2=.59, P=.029) with maternal 4-aminobiphenyl levels but not with fetal 4-aminobiphenyl levels. This study demonstrates that a potent tobacco-related carcinogen, 4-aminobiphenyl, or its active metabolite, N-hydroxy-4-aminobiphenyl, crosses the human placenta and binds to fetal hemoglobin in concentrations that are significantly higher in smokers than in nonsmokers. [J Natl Cancer Inst 83: 274–280, 1991]

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