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Journal of Cancer Research and Clinical Oncology logoLink to Journal of Cancer Research and Clinical Oncology
. 1997 Mar;123(3):141–151. doi: 10.1007/BF01214666

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

Helmut Daube 1, Gerhard Scherer 1,, Kirsten Riedel 1, Thomas Ruppert 1, Anthony R Tricker 1, Peter Rosenbaum 2, Franz Adlkofer 1
PMCID: PMC12201846  PMID: 9119879

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.

Key words: 8-Hydroxy-2′-deoxyguanosine, DNA adducts, Placenta, Smoking, Antioxidants

Abbreviations

8-OHdG

8-hydroxy-2′-deoxyguanosine

ETS

environmental tobacco smoke

References

  1. 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]
  2. 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 [PubMed] [Google Scholar]
  3. 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 [DOI] [PubMed] [Google Scholar]
  4. 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 [DOI] [PubMed] [Google Scholar]
  5. Claycamp HG (1992) Phenol sensitization of DNA to subsequent oxidative damage in 8-hydroxyguanine assays. Carcinogenesis 13:1289–1292 [DOI] [PubMed] [Google Scholar]
  6. 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 [DOI] [PubMed] [Google Scholar]
  7. 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 [DOI] [PubMed] [Google Scholar]
  8. 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 [DOI] [PubMed] [Google Scholar]
  9. 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 [DOI] [PubMed] [Google Scholar]
  10. Floyd RA (1990) The role of 8-hydroxyguanine in carcinogenesis. Carcinogenesis 11:1447–1450 [DOI] [PubMed] [Google Scholar]
  11. Foiles PG, Miglietta LM, Akerkar SA, Everson RB, Hecht SS (1988) Detection ofO6-methyldeoxyguanosine in human placental DNA. Cancer Res 48:4184–4188 [PubMed] [Google Scholar]
  12. 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 [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gupta RC (1985) Enhanced sensitivity of32P-postlabeling analysis of aromatic carcinogen-DNA adducts. Cancer Res 45:5656–5662 [PubMed] [Google Scholar]
  14. 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 [DOI] [PubMed] [Google Scholar]
  15. 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 [DOI] [PubMed] [Google Scholar]
  16. 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 [DOI] [PubMed] [Google Scholar]
  17. 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 [DOI] [PubMed] [Google Scholar]
  18. Harris CC (1991) Chemical and physical carcinogenesis: advances and perspectives for the 1990s. Cancer Res 51:5023–5044 [PubMed] [Google Scholar]
  19. 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 [DOI] [PubMed] [Google Scholar]
  20. Hatch MC, Warburton D, Santella RM (1990) Polycyclic aromatic hydrocarbon-DNA adducts in spontaneously aborted fetal tissue. Carcinogenesis 11:1673–1675 [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. 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 [DOI] [PubMed] [Google Scholar]
  23. 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 [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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 [DOI] [PubMed] [Google Scholar]
  25. Langone J, Gjika HB, Van Vunakis H (1973) Nicotine and its metabolites: Radioimmunoassay for nicotine and cotinine. Biochemistry 12:5025–5030 [DOI] [PubMed] [Google Scholar]
  26. 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 [DOI] [PubMed] [Google Scholar]
  27. 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 [DOI] [PubMed] [Google Scholar]
  28. 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 [DOI] [PubMed] [Google Scholar]
  29. 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 [DOI] [PubMed] [Google Scholar]
  30. 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 [PubMed] [Google Scholar]
  31. 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 [PubMed] [Google Scholar]
  32. 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 [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. 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]
  35. 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 [DOI] [PubMed] [Google Scholar]
  36. 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 [DOI] [PubMed] [Google Scholar]
  37. 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 [DOI] [PubMed] [Google Scholar]
  38. Poulsen HE, Loft S, Vistisen K (1993) Oxidative DNA damage after vigorous exercise in men. J Toxicol Environ Health 40:459 [DOI] [PubMed] [Google Scholar]
  39. 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 [PubMed] [Google Scholar]
  40. Reddy MV, Randerath K (1986) Nuclease P1-mediated enhancement of sensitivity of32P-postlabeling test for structurally diverse DNA adducts. Carcinogenesis 7:1543–1551 [DOI] [PubMed] [Google Scholar]
  41. 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 [DOI] [PubMed] [Google Scholar]
  42. Schectman G, Byrd JC, Gruchow HW (1989) The influence of smoking on vitamin C status in adults. Am J Publ Health 79:158–162 [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. 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 [PubMed] [Google Scholar]
  44. Shen HM, Ong CN, Lee BL, Shi CY (1995) Aflatoxin B1-induced 8-hydroxydeoxyguanosine formation in rat hepatic DNA. Carcinogenesis 16:419–422 [DOI] [PubMed] [Google Scholar]
  45. 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 [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. 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 [DOI] [PubMed] [Google Scholar]
  47. 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 [PubMed] [Google Scholar]
  48. Simic MG, Bergtold DS (1991) Dietary modulation of DNA damage in human. Mutat Res 250:17–24 [DOI] [PubMed] [Google Scholar]
  49. 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 [DOI] [PubMed] [Google Scholar]
  50. 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 [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. 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 [DOI] [PubMed] [Google Scholar]
  52. 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]
  53. 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 [DOI] [PubMed] [Google Scholar]
  54. 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 [DOI] [PubMed] [Google Scholar]
  55. 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 [DOI] [PubMed] [Google Scholar]
  56. 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 [DOI] [PubMed] [Google Scholar]
  57. 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 [DOI] [PubMed] [Google Scholar]
  58. 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 [DOI] [PubMed] [Google Scholar]
  59. 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 [PubMed] [Google Scholar]
  60. 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 [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. 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 [DOI] [PubMed] [Google Scholar]

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