title: The absence of interaction between drug metabolizing enzyme genotypes and maternal lifestyle factors on glycophorin A somatic mutation frequency levels in newborns.
abstract: Prenatal exposure to carcinogens results in newborn DNA damage which in turn is associated with impaired health conditions in both childhood and adulthood. The present study aimed to evaluate whether phase I and II biotransformation enzyme genetic polymorphisms in combination with environmental exposures during pregnancy result in elevated levels of newborn DNA damage. Maternal peripheral and umbilical cord blood samples from 406 mother/newborn pairs were genotyped for a panel of phase I/II metabolic enzymes (CYP1A1, CYP2E1, GSTM1, GSTT1 and NAT2) responsible for the metabolism of tobacco and lifestyle-related mutagens and carcinogens. DNA damage was measured by somatic cell mutation frequency at the glycophorin A (GPA) locus in newborns. No association with elevated somatic cell mutation frequency was observed between the combination of maternal/newborn genotypes and cigarette smoke or lifestyle exposures. The observed variation in newborn GPA frequency might be due to either environmental factors not assessed in this study or inter-individual differences in alternative metabolic or DNA repair pathways.
authors.affiliation: Center for Clinical Pharmacology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nukui
authors.forename: Richard D
authors.initials: RD
authors.lastname: Day
authors.forename: Heather A
authors.initials: HA
authors.lastname: Gordish-Dressman
authors.forename: Gail
authors.initials: G
authors.lastname: Harger
authors.forename: William L
authors.initials: WL
authors.lastname: Bigbee
authors.forename: Roberta B
authors.initials: RB
authors.lastname: Ness
authors.forename: Marjorie
authors.initials: M
authors.lastname: Romkes
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005838:Genotype; D006021:Glycophorins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D008431:Maternal-Fetal Exchange; D009035:Mothers; D009154:Mutation; D010597:Pharmacogenetics / Q000379:methods*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D012907:Smoking
chemical_list: D006021:Glycophorins