title: In utero DNA damage from environmental pollution is associated with somatic gene mutation in newborns.
abstract: Transplacental exposure to carcinogenic air pollutants from the combustion of fossil fuels is a growing health concern, given evidence of the heightened susceptibility of the fetus. These mutagenic/carcinogenic pollutants include aromatic compounds such as polycyclic aromatic hydrocarbons that bind to DNA, forming chemical-DNA adducts. We have investigated the genotoxic effects of transplacental exposure in humans by analyzing aromatic-DNA adducts and the frequency of gene mutations at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus in umbilical cord and maternal blood samples. Here we show, in a cross-sectional study of 67 mothers and 64 newborns from the Krakow Region of Poland, that aromatic-DNA adducts measured by (32)P-postlabeling are positively associated with HPRT mutant frequency in the newborns (beta = 0.56, P = 0.03) after controlling for exposure to tobacco smoke, diet, and socioeconomic status. In contrast to the fetus, HPRT mutations and DNA adducts do not reflect similar exposure periods in the mother, and the maternal biomarkers were not correlated. Adducts were higher in the newborn than the mother, indicating differential susceptibility of the fetus to DNA damage; but HPRT mutation frequency was 4-fold lower, consistent with the long lifetime of the biomarker. These results provide the first demonstration of a molecular link between somatic mutation in the newborn and transplacental exposure to common air pollutants, a finding that is relevant to cancer risk assessment.
authors.affiliation: Columbia University School of Public Health, New York, New York 10032, USA. Fpp1@columbia.edu
authors.forename: Frederica
authors.initials: F
authors.lastname: Perera
authors.forename: Karl
authors.initials: K
authors.lastname: Hemminki
authors.forename: Wieslaw
authors.initials: W
authors.lastname: Jedrychowski
authors.forename: Robin
authors.initials: R
authors.lastname: Whyatt
authors.forename: Ulka
authors.initials: U
authors.lastname: Campbell
authors.forename: Yanzhi
authors.initials: Y
authors.lastname: Hsu
authors.forename: Regina
authors.initials: R
authors.lastname: Santella
authors.forename: Richard
authors.initials: R
authors.lastname: Albertini
authors.forename: James P
authors.initials: JP
authors.lastname: O'Neill
mesh_terms: D000328:Adult; D003430:Cross-Sectional Studies; D018736:DNA Adducts; D004249:DNA Damage; D004252:DNA Mutational Analysis; D005314:Embryonic and Fetal Development; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D008431:Maternal-Fetal Exchange; D011044:Poland; D011247:Pregnancy; D014470:Umbilical Cord
chemical_list: D018736:DNA Adducts; D004785:Environmental Pollutants; D007041:Hypoxanthine Phosphoribosyltransferase