Determinants of polycyclic aromatic hydrocarbon-DNA adducts in human placenta.
To determine the relative contributions of tobacco smoking and P-450 metabolism (cytochrome P-450IAI) 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-DN A 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 [3.9 +/- 2.4 [corrected] (mean +/- SE) pmol 3-hydroxybenzo(a)pyrene mg protein-1 min-1], than among placentas from which BP-tetrols were not extracted (0.4 +/- 0.2 [corrected] 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.
Manchester
D K
DK
Children's Hospital Kempe Research Center, Department of Pediatrics, University of Colorado School of Medicine, Denver 80218.
Bowman
E D
ED
Parker
N B
NB
Caporaso
N E
NE
Weston
A
A
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000302:isolation & purification / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism*; D018736:DNA Adducts; D006801:Humans; D010920:Placenta / Q000737:chemistry / Q000378:metabolism*
D018736:DNA Adducts; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D004247:DNA