title: Polycyclic aromatic hydrocarbon-DNA adducts in human placenta and modulation by CYP1A1 induction and genotype.
abstract: This study investigated the relationship in human placenta between polycyclic aromatic hydrocabon (PAH)-DNA adduct levels and two biomarkers of cytochrome P4501A1 (CYP1A1): gene induction evidenced by CYP1A1 mRNA, and a genetic polymorphism, the CYP1A1 MspI RFLP. CYP1A1 codes for an inducible enzyme system that catalyzes the bioactivation of PAHs. Prior research found a high correlation in human lung tissue between CYP1A1 activity and DNA damage from PAHs. The CYP1A1 Mspi RFLP has been linked in some studies to risk of lung cancer. The relationships in human placenta between DNA damage, CYP1A1 activity and genotype have not been well characterized and may be relevant to risks from transplacental PAH exposure. The study cohort consisted of 70 newborns from Krakow, Poland, a city with elevated air pollution, and 90 newborns from nearby Limanowa, an area with lower air pollution but greater indoor coal use. Contrary to results seen previously in lung tissue, CYP1A1 mRNA was not significantly correlated with PAH-DNA adduct levels in the placenta. Smoking (self-reported maternal and infant plasma cotinine) was significantly associated with CYP1A1 mRNA levels (P < 0.01), but not with PAH-DNA adduct levels. Placental PAH-DNA adduct levels were significantly higher in infants with the CYP1A1 MspI restriction site compared with infants without the restriction site (P < 0.01), implicating a genetic factor in inter-individual variation in DNA damage in human placenta. Further studies are needed to determine the relevance of this finding to risk of transplacental carcinogenesis.
authors.affiliation: Columbia University School of Public Health, Division of Environmental Health Sciences, New York, NY 10032, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Whyatt
authors.forename: D A
authors.initials: DA
authors.lastname: Bell
authors.forename: W
authors.initials: W
authors.lastname: Jedrychowski
authors.forename: R M
authors.initials: RM
authors.lastname: Santella
authors.forename: S J
authors.initials: SJ
authors.lastname: Garte
authors.forename: G
authors.initials: G
authors.lastname: Cosma
authors.forename: D K
authors.initials: DK
authors.lastname: Manchester
authors.forename: T L
authors.initials: TL
authors.lastname: Young
authors.forename: T B
authors.initials: TB
authors.lastname: Cooper
authors.forename: R
authors.initials: R
authors.lastname: Ottman
authors.forename: F P
authors.initials: FP
authors.lastname: Perera
mesh_terms: D000328:Adult; D015415:Biomarkers; D015331:Cohort Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D018736:DNA Adducts / Q000378:metabolism*; D004790:Enzyme Induction; D005260:Female; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D010920:Placenta / Q000378:metabolism*; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism*; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons; D012333:RNA, Messenger; D019363:Cytochrome P-450 CYP1A1