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DNA adducts in human placenta in relation to tobacco smoke exposure and plasma antioxidant status

  • Original Paper
  • Experimental Oncology
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Abstract

The DNA adduct 8-hydroxy-2′-deoxyguanosine (8-OHdG) has been widely used as a biomarker for oxidative stress. Bulky DNA adducts, which are detectable by the32P-postlabelling method, provide evidence for exposure to and metabolic activation of large, mainly apolar compounds, e.g. polycyclic aromatic hydrocarbons. We determined both types of adducts in placental tissues of 30 term pregnancies and related the adduct levels to the exposure to tobacco smoke and the plasma antioxidant status. Urine and plasma cotinine concentrations were used to select 10 nonsmokers, 9 nonsmokers exposed to environmental tobacco smoke (ETS) and 11 smoking women. Placental levels of 8-OHdG were 0.84±0.11, 0.90±0.21 and 0.83±0.20/105 deoxyguanosine bases (dG) for nonsmokers, nonsmokers exposed to ETS and smokers, respectively. The differences between the groups were not significant. Smoking women had significantly lower plasma vitamin C and β-carotene concentrations than nonsmoking women or nonsmoking women exposed to environmental tobacco smoke. The 8-OHdG adduct level in placental DNA was inversely correlated with the plasma vitamin E concentration (r=−0.47,P<0.05). There was no association between placental 8-OHdG adducts and vitamin A, C and β-carotene in plasma. In total, 15 different adducts could be identified in the 30 placenta samples by the32P-postlabelling method. There was a strong inter-individual variation in both the number of adducts and adduct intensities. No smoking-related or vitamin-related effects on adduct patterns or intensities were found. Our findings suggests that, within the limits of the methods used, tobacco smoke exposure during pregnancy does not lead to a measurable increase in placental DNA adduct levels and that vitamin E appears to have a protective effect on placental 8-OHdG formation.

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Abbreviations

8-OHdG :

8-hydroxy-2′-deoxyguanosine

ETS :

environmental tobacco smoke

References

  • Albanese AA, Wein EH, Mata LA (1975) An improved method for determination of leucocyte and plasma ascorbic acid of man with applications to studies on nutritional needs and effects of cigarette smoking. Nutr Rep Int 12:271–289

    Google Scholar 

  • Biesalski H, Greiff H, Brodda K, Hafner G, Bässler KH (1986) Rapid determination of vitamin A (retinol) and vitamin F (α-tocopherol) in human serum by isocratic adsorption HPLC. Int J Vitam Nutr Res 56:319–327

    Google Scholar 

  • Brown RK, McBurney A, Lunec J, Kelly FJ (1995) Oxidative damage to DNA in patients with cystic fibrosis. Free Radic Biol Med 18:801–806

    Google Scholar 

  • Chow CK, Thacker RR, Changchit C, Bridges RB, Rehm SR, Humble J, Turbek J (1986) Lower levels of vitamin C and carotenes in plasma of cigarette smokers. J Am Coll Nutr 5:305–312

    Google Scholar 

  • Claycamp HG (1992) Phenol sensitization of DNA to subsequent oxidative damage in 8-hydroxyguanine assays. Carcinogenesis 13:1289–1292

    Google Scholar 

  • Comstock GW, Bush TL, Helzlsouer K (1992) Serum retinol, betacarotene, vitamin E, and selenium as related to subsequent cancer of specific sites. Am J Epidemiol 135:115–121

    Google Scholar 

  • Everson RB, Randerath E, Santella RM, Cefalo RC, Avitts TA, Randerath K (1986) Detection of smoking-related covalent DNA adducts in human placenta. Science 231:54–57

    Google Scholar 

  • Everson RB, Randerath E, Santella RM, Avitts TA, Weinstein IB, Randerath K (1988) Quantitative associations between DNA damage in human placenta and maternal smoking and birth weight. J Natl Cancer Inst 80:567–576

    Google Scholar 

  • Fischer-Neilsen A, Jeding IB, Loft S (1994) Radiation-induced formation of 8-hydroxy-2′-deoxyguanosine and its prevention by scavengers. Carcinogenesis 15:1609–1612

    Google Scholar 

  • Floyd RA (1990) The role of 8-hydroxyguanine in carcinogenesis. Carcinogenesis 11:1447–1450

    Google Scholar 

  • Foiles PG, Miglietta LM, Akerkar SA, Everson RB, Hecht SS (1988) Detection ofO 6-methyldeoxyguanosine in human placental DNA. Cancer Res 48:4184–4188

    Google Scholar 

  • Fraga CG, Motchnik PA, Shigenaga MK, Helbock HJ, Jacob RA, Ames BN (1991) Ascorbic acid protects against endogenous oxidative DNA damage in human sperm. Proc Natl Acad Sci USA 88:11003–11006

    Google Scholar 

  • Gupta RC (1985) Enhanced sensitivity of32P-postlabeling analysis of aromatic carcinogen-DNA adducts. Cancer Res 45:5656–5662

    Google Scholar 

  • Hågå P, Ek J, Kran S (1982) Plasma tocopherol levels and vitamin E/β-lipoprotein relationships during pregnancy and in cord blood. Am J Clin Nutr 36:1200–1204

    Google Scholar 

  • Halliwell B, Gutteridge JMC (1986) Oxygen free radicals and iron in relation to biology and medicine: some problems and concepts. Arch Biochem Biophys 246:501–514

    Google Scholar 

  • Hanaoka T, Tsugane S, Yamano Y, Takahashi T, Kasai H, Natori Y, Watanabe S (1993) Quantitative analysis of 8-hydroxyguanine in peripheral blood cells: An application for asbestosis patients. Int Arch Occup Environ Health 65:S215-S217

    Google Scholar 

  • Harats D, Ben-Naim M, Dabach Y, Hollander G, Havivi E, Ssein O, Stein Y (1990) Effect of vitamin C and E supplementation on susceptibility of plasma lipoproteins to peroxidation induced by acute smoking. Atherosclerosis 85:47–54

    Google Scholar 

  • Harris CC (1991) Chemical and physical carcinogenesis: advances and perspectives for the 1990s. Cancer Res 51:5023–5044

    Google Scholar 

  • Harris G, Bahir S, Winyard PG (1994) 7,8-Dihydro-8-oxo-2′-deoxyguanosine present in DNA is not simply an artefact of isolation. Carcinogenesis 15:411–413

    Google Scholar 

  • Hatch MC, Warburton D, Santella RM (1990) Polycyclic aromatic hydrocarbon-DNA adducts in spontaneously aborted fetal tissue. Carcinogenesis 11:1673–1675

    Google Scholar 

  • Heseker H, Schneider R, Moch KJ, Kohlmeier M, Kübler W (eds) (1994) Vitaminversorgung Erwachsener in der Bundesrepublik Deutschland, Band IV. Wissenschaftlicher Fachverlag, Niederkleen

    Google Scholar 

  • Holz O, Krause T, Scherer G, Schmidt-Preuβ U, Rüdiger HW (1990)32P-postlabelling analysis of DNA adducts in monocytes of smokers and passive smokers. Int Arch Occup Environ Health 62:299–303

    Google Scholar 

  • Inoue T, Mu Z, Sumikawa K, Adachi K, Okochi T (1993) Effect of physical exercise on the content of 8-hydroxydeoxyguanosine in nuclear DNA prepared from human lymphocytes. Jpn J Cancer Res 84:720–725

    Google Scholar 

  • Kiyosawa H, Suko M, Okudaira H, Murata K, Miyamoto T, Chung MH, Kasai H, Nishimura S (1990) Cigarette smoking induces formation of 8-hydroxydeoxyguanosine, one of the oxidative DNA damages in human peripheral leukocytes. Free Radic Res Commun 11:23–27

    Google Scholar 

  • Langone J, Gjika HB, Van Vunakis H (1973) Nicotine and its metabolites: Radioimmunoassay for nicotine and cotinine. Biochemistry 12:5025–5030

    Google Scholar 

  • Loft S, Vistisen K, Ewertz M, Tjønneland A, Overvad K, Poulsen HE (1992) Oxidative DNA damage estimated by 8-hydroxydeoxyguanosine excretion in humans: influence of smoking, gender and body mass index. Carcinogenesis 13:2241–2247

    Google Scholar 

  • Loft S, Fischer-Nielsen A, Jeding IB, Vistisen K, Poulsen HE (1993) 8-Hydroxydeoxyguanosine as a urinary biomarker of oxidative DNA damage. J Toxicol Environ Health 40:391–404

    Google Scholar 

  • Lu L-JW, Anderson LM, Jones AB, Moskal TJ, Salazar JJ, Hokanson JA, Rice JM (1993) Persistence, gestation stage-dependent formation and interrelationship of benzo[a]pyrene-induced DNA adducts in mothers, placentae and fetuses ofErythrocebus patas monkeys. Carcinogenesis 14:1805–1813

    Google Scholar 

  • Manchester DK, Wilson VL, Hsu I-C, Choi J-S, Parker NB, Mann DL, Weston A, Harris CC (1990) Shynchronous fluorescence spectroscopic, immunoaffinity chromatographic and32P-postlabeling analysis of human placental DNA known to contain benzo[a]pyrene diol epoxide adducts. Carcinogenesis 11: 553–559

    Google Scholar 

  • Manchester DK, Bowman ED, Parker NB, Caporaso NE, Weston A (1992) Determinants of polycyclic aromatic hydrocarbon-DNA adducts in human placenta. Cancer Res 52:1499–1503

    Google Scholar 

  • Mandach U von, Huch R, Huch A (1993) Maternal and cord serum vitamin E levels in normal and abnormal pregnancy. Int J Vitam Nutr Res 63:26–32

    Google Scholar 

  • Masuda T, Miyasaka N, Kato T, Ueno Y (1991) Formation of the 8-hydroxyguanosine moiety in hepatic DNA of mice orally administered with luteoskyrin, a bis-anthraquinoid mycotoxin. Toxicol Lett 58:287–295

    Google Scholar 

  • Norkus EP, Hsu H, Cehelsky MR (1987) Effect of cigarette smoking on the vitamin C status of pregnant women and their offspring. Ann N Y Acad Sci 498:500–501

    Google Scholar 

  • Norkus EP, Hsu HW, Leighton LS, Cehelsky MR (1989) Relationship between cigarette smoking and plasma-levels of vitamin E and β-carotene in pregnant women and newborn infants. FASEB J 3: A 766

    Google Scholar 

  • Ogawa T, Higashi S, Kawarada Y, Mizumoto R (1995) Role of reactive oxygen in synthetic estrogen induction of hepatocellular carcinomas in rats and preventive effect of vitamins. Carcinogenesis 16:831–836

    Google Scholar 

  • Okamoto K, Toyokuni S, Uchida K, Ogawa O, Takenewa J, Kakehi Y, Kinoshita H, Hattori-Nakakuki Y, Hiai H, Yoshida O (1994) Formation of 8-hydroxy-2′-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins in human renal-cell carcinoma. Int J Cancer 58:825–829

    Google Scholar 

  • Pasanen M, Pelkonen O (1990) Xenobiotic and steroid-metabolizing monooxygenases catalysed by cytochromeP450 and glutathioneS-transferase conjugations in the human placenta and their relationships to maternal cigarette smoking. Placenta 11:75–85

    Google Scholar 

  • Poulsen HE, Loft S, Vistisen K (1993) Oxidative DNA damage after vigorous exercise in men. J Toxicol Environ Health 40:459

    Google Scholar 

  • Randerath E, Avitts TA, Reddy MV, Miller RH, Everson RB, Randerath K (1986) Comparative32P-analysis of cigarette smoke-induced DNA damage in human tissues and mouse skin. Cancer Res 46:5869–5877

    Google Scholar 

  • Reddy MV, Randerath K (1986) Nuclease P1-mediated enhancement of sensitivity of32P-postlabeling test for structurally diverse DNA adducts. Carcinogenesis 7:1543–1551

    Google Scholar 

  • Reddy MV, Kenny PC, Randerath K (1990)32P-assay of DNA adducts in white blood cells and placentas of pregnant women: lack of residential wood combustion-related adducts but presence of tissue-specific endogenous adducts. Teratogenesis Carcinog Mutagen 10:373–384

    Google Scholar 

  • Schectman G, Byrd JC, Gruchow HW (1989) The influence of smoking on vitamin C status in adults. Am J Publ Health 79:158–162

    Google Scholar 

  • Scherer G, Jarczyk L, Heller W-D, Biber A, Neurath GB, Adlkofer F (1988) Pharmacokinetics of nicotine, cotinine, and 3′-hydroxycotinine in cigarette smokers. Klin Wochenschr 66:5–11

    Google Scholar 

  • Shen HM, Ong CN, Lee BL, Shi CY (1995) Aflatoxin B1-induced 8-hydroxydeoxyguanosine formation in rat hepatic DNA. Carcinogenesis 16:419–422

    Google Scholar 

  • Shigenaga MK, Gimeno CJ, Ames BN (1989) Urinary 8-hydroxy-2′-deoxyguanosine as a biological marker of in vivo oxidative DNA damage. Proc Natl Acad Sci USA 86:9697–9701

    Google Scholar 

  • Shigenaga MK, Aboujaoude EN, Chen Q, Ames BN (1994) Assays of oxidative DNA damage biomarkers 8-oxo-2′-deoxyguanosine and 8-oxoguanine in nuclear DNA and biological fluids by high-performance liquid chomatography with electrochemical detection. Methods Enzymol 234:16–33

    Google Scholar 

  • Shimoda R, Nagashima M, Sakamoto M, Yamaguchi N, Hirohashi S, Yokota J, Kasai H (1994) Increased formation of oxidative DNA damage, 8-hydroxyguanosine, in human livers with chronic hepatitis. Cancer Res 54:3171–3172

    Google Scholar 

  • Simic MG, Bergtold DS (1991) Dietary modulation of DNA damage in human. Mutat Res 250:17–24

    Google Scholar 

  • Stryker WS, Kaplan LA, Stein EA, Stampfer MJ, Sober A, Willett WC (1988) The relation of diet, cigarette smoking, and alcohol consumption to plasma beta-carotene and alpha-tocopherol levels. Am J Epidemiol 127:283–296

    Google Scholar 

  • Subar AF, Harlan LC, Mattson ME (1990) Food and nutrient intake differences between smokers and non-smokers in the US. Am J Publ Health 80:1323–1329

    Google Scholar 

  • Suzuki J, Inoue Y, Suzuki S (1995) Changes in the urinary excretion level of 8-hydroxyguanine by exposure to reactive oxygengenerating substances. Free Radic Biol Med 18:431–436

    Google Scholar 

  • Taffe BG, Sheilds PG, Kasai H, Povey AC, Yeager H, Trivers G, Nishimura S, Harris CC, Wilson VL (1991) Analysis of 8-hydroxydeoxyguanosine DNA adducts in humans following exposure to oxidants; an interlaboratory study. Proc Am Assoc Cancer Res 32:225

    Google Scholar 

  • Takagi A, Sai K, Umemura T, Hasegawa R, Kurokawa Y (1995) Inhibitory effects of vitamin E and ellagic acid on 8-hydroxydeoxyguanosine formation in liver nuclear DNA of rats treated with 2-nitropropane. Cancer Lett 91:139–144

    Google Scholar 

  • Takeuchi T, Nakajima M, Ohta Y, Mure K, Takeshita T, Morimoto K (1994) Evaluation of 8-hydroxyguanosine, a typical oxidative DNA damage, in human leukocytes. Carcinogenesis 15:1519–1523

    Google Scholar 

  • Umegaki K, Ikegami S, Ichikawa T (1993) Influence of dietary vitamin E on the 8-hydroxydeoxyguanosine levels in rat liver DNA. J Nutr Sci Vitaminol 39:303–310

    Google Scholar 

  • Uotila J, Tuimala R, Aarnio T, Pyykkö K, Ahotupa M (1991) Lipid peroxidation products, selenium-dependent glutathione peroxidase and vitamin E in normal pregnancy. Eur J Obstet Gynecol Reprod Biol 42:95–100

    Google Scholar 

  • Van Poppel G, Poulsen H, Loft S, Verhagen H (1995) No influence of beta-carotene on oxidative DNA damage in male smokers. J Natl Cancer Inst 87:310–311

    Google Scholar 

  • Wang Y, Walsh SW, Guo J, Zhang J (1991) The imbalance between thromboxane and prostacyclin in preeclampsia is associated with an imbalance between lipid peroxides and vitamin E in maternal blood. Am J Obstet Gynecol 165:1695–1700

    Google Scholar 

  • Whyatt RM, Garte SJ, Cosma G, Bell DA, Jedrychowski W, Wahrendorf J, Randall MC, Cooper TB, Ottman R, Tang D, Tsai W-Y, Dickey CP, Manchester NK, Crofts F, Perera FP (1995) CYP1A1 messenger RNA levels in placental tissue as a biomarker of environmental exposure. Cancer Epidemiol Biomarkers Prev 4:147–153

    Google Scholar 

  • Yamamoto F, Kasai H, Bessho T, Chung M-H, Inoue H, Ohtsuka E, Hori T, Nishimura S (1992) Ubiquitous presence in mammalian cells of enzymatic activity specifically cleaving 8-hydroxyguanine-containing DNA. Jpn J Cancer Res 83:351–357

    Google Scholar 

  • Yin B, Whyatt RM, Perera FP, Randall MC, Cooper TB, Santella RM (1995) Determination of 8-hydroxydeoxyguanosine by an immunoaffinity chromatography-monoclonal antibody-based ELISA. Free Radic Res Commun 18:1023–1032

    Google Scholar 

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Daube, H., Scherer, G., Riedel, K. et al. DNA adducts in human placenta in relation to tobacco smoke exposure and plasma antioxidant status. J Cancer Res Clin Oncol 123, 141–151 (1997). https://doi.org/10.1007/BF01214666

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  • DOI: https://doi.org/10.1007/BF01214666

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