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Determinants of Polycyclic Aromatic Hydrocarbon-DNA Adducts in Human Placenta¹

The Children's Hospital Kempe Research Center, Department of Pediatrics and Pharmacology, University of Colorado School of Medicine, Denver, Colorado 80218 [D. K. M., N. B. P.], and Laboratory of Human Carcinogenesis [E. D. B., A. W.] and Environmental Epidemiology Branch [N. E. C.], National Cancer Institute, NIH, Bethesda, Maryland 20892

To determine the relative contributions of tobacco smoking and P-450 metabolism (cytochrome P-450_IAI) in the formation of benzo(a)pyrenediol-epoxide and other polycyclic aromatic hydrocarbon-DNA adducts in vivo, 16 human placentas were assayed for aryl hydrocarbon hydroxylase activity and (±)r-7,t-8-dihydroxy-c-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene-DNA adduct levels. Immunoaffinity chromatography columns, conjugated with monoclonal antibodies raised against benzo(a)-pyrene-diol-epoxide-deoxyguanosine, were used to concentrate polycyclic aromatic hydrocarbon-DNA adducted nucleotides, and synchronous fluorescence spectroscopy was used specifically to detect r-7,t-8,t-9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BP-tetrol) extracted from acid hydrolysates of immunoconcentrated materials. Data were analyzed for associations with maternal dietary and smoking habits, umbilical cord blood cotinine levels, and placental aryl hydrocarbon hydroxylase levels. Complex mixtures of fluorescent materials were present in organic solvent extracts of acid hydrolysates of immunoconcentrated nucleotide-adducts from all placentas with patterns of fluorescence that may be associated with tobacco smoking determined by generation of spectral fluorescence excitation-emission matrices. BP-tetrols were detected in extracts from 8 placentas: 5 of 7 from smokers and 3 of 9 from nonsmokers. Placental aryl hydrocarbon hydroxylase activity was significantly higher in placentas from which BP-tetrols were extracted [13.0 ± 4.0 (mean ± SE) pmol 3-hydroxybenzo(a)pyrene mg protein^–1 min^–1], than among placentas from which BP-tetrols were not extracted (1.3 ± 3.7 pmol 3-hydroxybenzo(a)pyrene mg protein^–1 min^–1) (P = 0.03, Student's t test). This association was independent of maternal smoking or umbilical cord blood cotinine levels. These results indicate that while maternal tobacco smoking is associated with the accumulation of putative, but as yet unidentified, polycyclic aromatic hydrocarbon-DNA adducts in placenta, metabolic capacity appears to be the principal determinant for the (±)r-7,t-8-dihydroxy-c-9,10 epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene-DNA adduct levels detected.

¹ This work was supported, in part, by the March of Dimes Reproductive Hazards in the Workplace, Home and Environment, Grant 17–115; and by a grant (RR-69) from the General Clinical Research Centers Program of the Division of Research Resources, NIH.

² To whom requests for reprints should be addressed, at: Room 2C16, Building 37, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

Received 9/18/91. Accepted 1/ 8/92.

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