Three classes of DNA damage were assessed in human placentas collected (2000-2004) from 51 women living in the Teplice region of the Czech Republic, a mining area considered to have some of the worst environmental pollution in Europe in the 1980s. Polycyclic aromatic hydrocarbon (PAH)-DNA adducts were localized and semiquantified using immunohistochemistry (IHC) and the Automated Cellular Imaging System (ACIS). More generalized DNA damage was measured both by (32)P-postlabeling and by abasic (AB) site analysis. Placenta stained with antiserum elicited against DNA modified with 7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPDE) revealed PAH-DNA adduct localization in nuclei of the cytotrophoblast (CT) cells and syncytiotrophoblast (ST) knots lining the chorionic villi. The highest levels of DNA damage, 49-312 PAH-DNA adducts/10(8) nucleotides, were found by IHC/ACIS in 14 immediately fixed placenta samples. An additional 37 placenta samples were stored frozen before fixation and embedding, and because PAH-DNA adducts were largely undetectable in these samples, freezing was implicated in the loss of IHC signal. The same placentas (n = 37) contained 1.7-8.6 stable/bulky DNA adducts/10(8) nucleotides and 0.6-47.2 AB sites/10(5) nucleotides. For all methods, there was no correlation among types of DNA damage and no difference in extent of DNA damage between smokers and nonsmokers. Therefore, the data show that DNA from placentas obtained in Teplice contained multiple types of DNA damage, which likely arose from various environmental exposures. In addition, PAH-DNA adducts were present at high concentrations in the CT cells and ST knots of the chorionic villi.

Carcinogen DNA Interactions Section LCBG Center for Cancer Research National Cancer Institute NIH Bethesda Maryland USA

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Arnould JP, Verhoest P, Bach V, Libert JP, Belegaud J. Detection of benzo[a]pyrene-DNA adducts in human placenta and umbilical cord blood. Hum Exp Toxicol. 1997;16:716–721. PubMed

Binkova B, Cerna M, Pastorkova A, Jelinek R, Benes I, Novak J, Sram RJ. Biological activities of organic compounds adsorbed onto ambient air particles: comparison between the cities of Teplice and Prague during the summer and winter seasons 2000–2001. Mutat Res. 2003;525:43–59. PubMed

Bostrom CE, Gerde P, Hanberg A, Jernstrom B, Johansson C, Kyrklund T, Rannug A, Tornqvist M, Victorin K, Westerholm R. Cancer risk assessment, indicators, and guidelines for polycyclic aromatic hydrocarbons in the ambient air. Environ Health Perspect. 2002;110:451–488. PubMed PMC

Cross JC, Nakano H, Natale DR, Simmons DG, Watson ED. Branching morphogenesis during development of placental villi. Differentiation. 2006;74:393–401. PubMed

Dejmek J. The impact of polycyclic aromatic hydrocarbons and fine particles on pregnancy outcome. Environ Health Perspect. 2000;108:1159–1164. PubMed PMC

Dejmek J, Selevan SG, Benes I, Solansky I, Sram RJ. Fetal growth and maternal exposure to particulate matter during pregnancy. Environ Health Perspect. 1999;107:475–480. PubMed PMC

Divi RL, Beland FA, Fu PP, Von Tungeln LS, Schoket B, Camara JE, Ghei M, Rothman N, Sinha R, Poirier MC. Highly sensitive chemiluminescence immunoassay for benzo[a]pyrene-DNA adducts: validation by comparison with other methods, and use in human biomonitoring. Carcinogenesis. 2002;23:2043–2049. PubMed

Gorelick NJ, Wogan GN. Fluoranthene-DNA adducts: identification and quantification by an HPLC-32P-postlabeling method. Carcinogenesis. 1989;10:1567–1577. PubMed

Gyorffy E, Anna L, Kovacs K, Rudnai P, Schoket B. Correlation between biomarkers of human exposure to genotoxins with focus on carcinogen-DNA adducts. Mutagenesis. 2008;23:1–18. PubMed

John K, Ragavan N, Pratt MM, Singh PB, Al-Buheissi S, Matanhelia SS, Phillips DH, Poirier MC, Martin FL. Quantification of phase I/II metabolizing enzyme gene expression and polycyclic aromatic hydrocarbon-DNA adduct levels in human prostate. The Prostate. 2009;69:505–519. PubMed PMC

Kang DH, Rothman N, Poirier MC, Greenberg A, Hsu CH, Schwartz BS, Baser ME, Groopman JD, Weston A, Strickland PT. Interindividual differences in the concentration of 1-hydroxypyrene-glucuronide in urine and polycyclic aromatic hydrocarbon-DNA adducts in peripheral white blood cells after charbroiled beef consumption. Carcinogenesis. 1995;16:1079–1085. PubMed

King LC, Adams L, Allison J, Kohan MJ, Nelson G, Desai D, Amin S, Ross JA. A quantitative comparison of dibenzo[a,l]pyrene-DNA adduct formation by recombinant human cytochrome P450 microsomes. Mol Carcinog. 1999;26:74–82. PubMed

King LC, George M, Gallagher JE, Lewtas J. Separation of 32P-postlabeled DNA adducts of polycyclic aromatic hydrocarbons and nitrated polycyclic aromatic hydrocarbons by HPLC. Chem Res Toxicol. 1994;7:503–510. PubMed

King LC, Kohan MJ, Brooks L, Nelson GB, Ross JA, Allison J, Adams L, Desai D, Amin S, Padgett W, Lambert GR, Richard AM, Nesnow S. An evaluation of the mutagenicity, metabolism, and DNA adduct formation of 5-nitrobenzo[b]naphtho[2,1-d]thiophene. Chem Res Toxicol. 2001;14:661–671. PubMed

Lewtas J. Air pollution combustion emissions: Characterization of causative agents and mechanisms associated with cancer, reproductive, and cardiovascular effects. Mutat Res. 2007;636:95–133. PubMed

Manchester DK, Weston A, Choi JS, Trivers GE, Fennessey PV, Quintana E, Farmer PB, Mann DL, Harris CC. Detection of benzo[a]pyrene diol epoxide-DNA adducts in human placenta. Proc Natl Acad Sci U S A. 1988;85:9243–9247. PubMed PMC

Marafie EM, Marafie I, Emery SJ, Waters R, Jones NJ. Biomonitoring the human population exposed to pollution from the oil fires in Kuwait: Analysis of placental tissue using P-32-postlabeling. Environ Mol Mutagen. 2000;36:274–282. PubMed

Maynard S, Schurman SH, Harboe C, de Souza-Pinto NC, Bohr VA. Base excision repair of oxidative DNA damage and association with cancer and aging. Carcinogenesis. 2009;30:2–10. PubMed PMC

McDorman KS, Pachkowski BF, Nakamura J, Wolf DC, Swenberg JA. Oxidative DNA damage from potassium bromate exposure in Long-Evans rats is not enhanced by a mixture of drinking water disinfection by-products. Chem Biol Interact. 2005;152:107–117. PubMed

Phillips DH. Smoking-related DNA and protein adducts in human tissues. Carcinogenesis. 2002;23:1979–2004. PubMed

Poirier MC, Santella R, Weinstein IB, Grunberger D, Yuspa SH. Quantitation of benzo(a)pyrene-deoxyguanosine adducts by radioimmunoassay. Cancer Res. 1980;40:412–416. PubMed

Poirier MC, Weston A, Schoket B, Shamkhani H, Pan CF, McDiarmid MA, Scott BG, Deeter DP, Heller JM, Jacobson-Kram D, Rothman N. Biomonitoring of United States Army soldiers serving in Kuwait in 1991. Cancer Epidemiol Biomarkers Prev. 1998;7:545–551. PubMed

Pratt MM, Sirajuddin P, Poirier MC, Schiffman M, Glass AG, Scott DR, Rush BB, Olivero OA, Castle PE. Polycyclic aromatic hydrocarbon-DNA adducts in cervix of women infected with carcinogenic human papillomavirus types: An immunohistochemistry study. Mutat Res. 2007;624:114–123. PubMed PMC

Ramesh A, Walker SA, Hood DB, Guillen MD, Schneider K, Weyand EH. Bioavailability and risk assessment of orally ingested polycyclic aromatic hydrocarbons. Int J Toxicol. 2004;23:301–333. PubMed

Rothman N, Correa-Villasenor A, Ford DP, Poirier MC, Haas R, Hansen JA, O'Toole T, Strickland PT. Contribution of occupation and diet to white blood cell polycyclic aromatic hydrocarbon-DNA adducts in wildland firefighters. Cancer Epidemiol Biomarkers Prev. 1993a;2:341–347. PubMed

Rothman N, Poirier MC, Baser ME, Hansen JA, Gentile C, Bowman ED, Strickland PT. Formation of polycyclic aromatic hydrocarbon-DNA adducts in peripheral white blood cells during consumption of charcoal-broiled beef. Carcinogenesis. 1990;11:1241–1243. PubMed

Rothman N, Poirier MC, Haas RA, Correa-Villasenor A, Ford P, Hansen JA, O'Toole T, Strickland PT. Association of PAH-DNA adducts in peripheral white blood cells with dietary exposure to polyaromatic hydrocarbons. Environ Health Perspect. 1993b;99:265–267. PubMed PMC

Sanyal MK, Mercan D, Belanger K, Santella RM. DNA adducts in human placenta exposed to ambient environment and passive cigarette smoke during pregnancy. Birth Defects Res Part A Clin Mol Teratol. 2007;79:289–294. PubMed

Sram RJ. Teplice Program: Impact of air pollution on human health. Prague: Academia; 2001. pp. 1–318. PubMed PMC

Sram RJ, Binkova B, Rossner P, Rubes J, Topinka J, Dejmek J. Adverse reproductive outcomes from exposure to environmental mutagens. Mutat Res. 1999;428:203–215. PubMed

Swartz CD, King LC, Nesnow S, Umbach DM, Kumar S, Demarini DM. Mutagenicity, stable DNA adducts, and abasic sites induced in Salmonella by phenanthro[3,4-b]- and phenanthro[4,3-b]thiophenes, sulfur analogs of benzo[c]phenanthrene. Mutat Res. 2009;661:47–56. PubMed PMC

Topinka J, Binkova B, Mrackova G, Stavkova Z, Benes I, Dejmek J, Lenicek J, Sram RJ. DNA adducts in human placenta as related to air pollution and to GSTM1 genotype. Mutat Res. 1997;390:59–68. PubMed

van Gijssel HE, Divi RL, Olivero OA, Roth MJ, Wang GQ, Dawsey SM, Albert PS, Qiao YL, Taylor PR, Dong ZW, Schrager JA, Kleiner DE, Poirier MC. Semiquantitation of polycyclic aromatic hydrocarbon-DNA adducts in human esophagus by immunohistochemistry and the automated cellular imaging system. Cancer Epidemiol Biomarkers Prev. 2002;11:1622–1629. PubMed

van Gijssel HE, Schild LJ, Watt DL, Roth MJ, Wang GQ, Dawsey SM, Albert PS, Qiao YL, Taylor PR, Dong ZW, Poirier MC. Polycyclic aromatic hydrocarbon-DNA adducts determined by semiquantitative immunohistochemistry in human esophageal biopsies taken in 1985. Mutat Res. 2004;547:55–62. PubMed

Weston A, Manchester DK, Poirier MC, Choi JS, Trivers GE, Mann DL, Harris CC. Derivative fluorescence spectral analysis of polycyclic aromatic hydrocarbon-DNA adducts in human placenta. Chem Res Toxicol. 1989;2:104–108. PubMed

Weyand EH, Rice JE, LaVoie EJ. 32P-postlabeling analysis of DNA adducts from non-alternant PAH using thin-layer and high performance liquid chromatography. Cancer Lett. 1987;37:257–266. PubMed

Whyatt RM, Bell DA, Jedrychowski W, Santella RM, Garte SJ, Cosma G, Manchester DK, Young TL, Cooper TB, Ottman R, Perera FP. Polycyclic aromatic hydrocarbon- DNA adducts in human placenta and modulation by CYP1A1 induction and genotype. Carcinogenesis. 1998;19:1389–1392. PubMed

Xiao R, Su Y, Simmen RC, Simmen FA. Dietary soy protein inhibits DNA damage and cell survival of colon epithelial cells through attenuated expression of fatty acid synthase. Am J Physiol Gastrointest Liver Physiol. 2008;294:G868–G876. PubMed