HPLC and GC/MS determination of 4-aminobiphenyl haemoglobin adducts in fetuses exposed to the tobacco smoke carcinogen in utero

Abstract

Maternal-fetal exchange of the potent tobacco-related human carcinogen, 4-aminobiphenyl, was studied in women nonsmokers and in women smokers as well as in the corresponding fetuses during pregnancy. Smoking status of the women in the study was assessed via questionnaire and measurement by immunoassay of serum cotinine in maternal and fetal blood samples. 4-Aminobiphenyl was extracted from both maternal and fetal blood samples using organic solvent extractions and the released amine was qualitatively and quantitatively characterized by analysis of the samples by high pressure liquid chromatography (HPLC) and gas chromatography coupled with mass spectrometry (GC/MS). Background levels (pg 4-aminobiphenyl/g haemoglobin) of 4-aminobiphenyl-haemoglobin adducts were detected in maternal nonsmokers (mean ± S.D; 29.6 ± 16.2 (GC/MS); 23.7 ± 13.5 (HPLC) and in fetal samples (14.0 ± 6.5 (GC/MS); 10.0 ± 4.6 (HPLC)). Elevated levels of 4-aminobiphenyl-haemoglobin adducts were found in maternal smokers (488 ± 174 (GC/MS); 423 ± 154 (HPLC)) as well as in the corresponding fetal blood samples (244 ± 91 (GC/MS); 197 ± 77 (HPLC). This study confirms that a potent tobacco-related carcinogen, 4-aminobiphenyl, crosses the human placenta and binds to fetal haemoglobin in significantly higher concentrations in smokers when compared to nonsmokers.