Skip to main content
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1999 Jun;107(6):469–474. doi: 10.1289/ehp.107-1566580

8-hydroxy-2'-deoxyguanosine, a major mutagenic oxidative DNA lesion, and DNA strand breaks in nasal respiratory epithelium of children exposed to urban pollution.

L Calderón-Garcidueñas 1, L Wen-Wang 1, Y J Zhang 1, A Rodriguez-Alcaraz 1, N Osnaya 1, A Villarreal-Calderón 1, R M Santella 1
PMCID: PMC1566580  PMID: 10339447

Abstract

Southwest metropolitan Mexico City children are repeatedly exposed to high levels of a complex mixture of air pollutants, including ozone, particulate matter, aldehydes, metals, and nitrogen oxides. We explored nasal cell 8-hydroxy-2'-deoxyguanosine (8-OHdG), a major mutagenic lesion producing G-->T transversion mutations, using an immunohistochemical method, and DNA single strand breaks (ssb) using the single cell gel electrophoresis assay as biomarkers of oxidant exposure. Nasal biopsies from the posterior inferior turbinate were examined in children in grades one through five, including 12 controls from a low-polluted coastal town and 87 Mexico City children. Each biopsy was divided for the 8-OHdG and DNA ssb assays. There was an age-dependent increase in the percentage of nasal cells with DNA tails > 10 microm in Mexico City children: 19 +/- 9% for control cells, and 43 +/- 4, 50 +/- 16, 56 +/- 17, 60 +/- 17 and 73 +/- 14%, respectively, for first through fifth graders (p < 0.05). Nasal ssb were significantly higher in fifth graders than in first graders (p < 0.05). Higher levels (2.3- to 3-fold) of specific nuclear staining for 8-OHdG were observed in exposed children as compared to controls (p < 0.05). These results suggest that DNA damage is present in nasal epithelial cells in Mexico City children. Persistent oxidative DNA damage may ultimately result in a selective growth of pr eneoplastic nasal initiated cells in this population and the potential for nasal neoplasms may increase with age. The combination of 8-OHdG and DNA ssb should be useful for monitoring oxidative damage in people exposed to polluted atmospheres.

Full text

PDF
469

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ames B. N. Endogenous oxidative DNA damage, aging, and cancer. Free Radic Res Commun. 1989;7(3-6):121–128. doi: 10.3109/10715768909087933. [DOI] [PubMed] [Google Scholar]
  2. Ames B. N., Gold L. S., Willett W. C. The causes and prevention of cancer. Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5258–5265. doi: 10.1073/pnas.92.12.5258. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ames B. N., Shigenaga M. K., Hagen T. M. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):7915–7922. doi: 10.1073/pnas.90.17.7915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baez A. P., Belmont R., Padilla H. Measurements of formaldehyde and acetaldehyde in the atmosphere of Mexico City. Environ Pollut. 1995;89(2):163–167. doi: 10.1016/0269-7491(94)00059-m. [DOI] [PubMed] [Google Scholar]
  5. Bartsch H., Hietanen E. The role of individual susceptibility in cancer burden related to environmental exposure. Environ Health Perspect. 1996 May;104 (Suppl 3):569–577. doi: 10.1289/ehp.96104s3569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Blake D. R., Rowland F. S. Urban leakage of liquefied petroleum gas and its impact on Mexico city air quality. Science. 1995 Aug 18;269(5226):953–956. doi: 10.1126/science.269.5226.953. [DOI] [PubMed] [Google Scholar]
  7. Bogdanffy M. S., Mathison B. H., Kuykendall J. R., Harman A. E. Critical factors in assessing risk from exposure to nasal carcinogens. Mutat Res. 1997 Oct 31;380(1-2):125–141. [PubMed] [Google Scholar]
  8. Borm P. J., Knaapen A. M., Schins R. P., Godschalk R. W., Schooten F. J. Neutrophils amplify the formation of DNA adducts by benzo[a]pyrene in lung target cells. Environ Health Perspect. 1997 Sep;105 (Suppl 5):1089–1093. doi: 10.1289/ehp.97105s51089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Calderon-Garciduenas L., Osnaya-Brizuela N., Ramirez-Martinez L., Villarreal-Calderon A. DNA strand breaks in human nasal respiratory epithelium are induced upon exposure to urban pollution. Environ Health Perspect. 1996 Feb;104(2):160–168. doi: 10.1289/ehp.96104160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Calderon-Garcidueñas L., Osorno-Velazquez A., Bravo-Alvarez H., Delgado-Chavez R., Barrios-Marquez R. Histopathologic changes of the nasal mucosa in southwest Metropolitan Mexico City inhabitants. Am J Pathol. 1992 Jan;140(1):225–232. [PMC free article] [PubMed] [Google Scholar]
  11. Calderón-Garcidueñas L., Osnaya N., Rodríguez-Alcaraz A., Villarreal-Calderón A. DNA damage in nasal respiratory epithelium from children exposed to urban pollution. Environ Mol Mutagen. 1997;30(1):11–20. doi: 10.1002/(sici)1098-2280(1997)30:1<11::aid-em3>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  12. Calderón-Garcidueñas L., Rodriguez-Alcaraz A., García R., Ramírez L., Barragan G. Nasal inflammatory responses in children exposed to a polluted urban atmosphere. J Toxicol Environ Health. 1995 Aug;45(4):427–437. doi: 10.1080/15287399509532006. [DOI] [PubMed] [Google Scholar]
  13. Cerutti P. A. Oxy-radicals and cancer. Lancet. 1994 Sep 24;344(8926):862–863. doi: 10.1016/s0140-6736(94)92832-0. [DOI] [PubMed] [Google Scholar]
  14. Cerutti P., Ghosh R., Oya Y., Amstad P. The role of the cellular antioxidant defense in oxidant carcinogenesis. Environ Health Perspect. 1994 Dec;102 (Suppl 10):123–129. doi: 10.1289/ehp.94102s10123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Chen Q., Marsh J., Ames B., Mossman B. Detection of 8-oxo-2'-deoxyguanosine, a marker of oxidative DNA damage, in culture medium from human mesothelial cells exposed to crocidolite asbestos. Carcinogenesis. 1996 Nov;17(11):2525–2527. doi: 10.1093/carcin/17.11.2525. [DOI] [PubMed] [Google Scholar]
  16. Clayson D. B., Mehta R., Iverson F. International Commission for Protection Against Environmental Mutagens and Carcinogens. Oxidative DNA damage--the effects of certain genotoxic and operationally non-genotoxic carcinogens. Mutat Res. 1994 Feb;317(1):25–42. doi: 10.1016/0165-1110(94)90010-8. [DOI] [PubMed] [Google Scholar]
  17. Cochrane C. G. Mechanisms of oxidant injury of cells. Mol Aspects Med. 1991;12(2):137–147. doi: 10.1016/0098-2997(91)90009-b. [DOI] [PubMed] [Google Scholar]
  18. Collins A. R., Dobson V. L., Dusinská M., Kennedy G., Stetina R. The comet assay: what can it really tell us? Mutat Res. 1997 Apr 29;375(2):183–193. doi: 10.1016/s0027-5107(97)00013-4. [DOI] [PubMed] [Google Scholar]
  19. Collins A. R., Dusinská M., Gedik C. M., Stetina R. Oxidative damage to DNA: do we have a reliable biomarker? Environ Health Perspect. 1996 May;104 (Suppl 3):465–469. doi: 10.1289/ehp.96104s3465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Collins A. R., Duthie S. J., Fillion L., Gedik C. M., Vaughan N., Wood S. G. Oxidative DNA damage in human cells: the influence of antioxidants and DNA repair. Biochem Soc Trans. 1997 Feb;25(1):326–331. doi: 10.1042/bst0250326. [DOI] [PubMed] [Google Scholar]
  21. Dahlhaus M., Almstadt E., Henschke P., Lüttgert S., Appel K. E. Induction of 8-hydroxy-2-deoxyguanosine and single-strand breaks in DNA of V79 cells by tetrachloro-p-hydroquinone. Mutat Res. 1995 Jun;329(1):29–36. doi: 10.1016/0027-5107(95)00014-a. [DOI] [PubMed] [Google Scholar]
  22. Darley-Usmar V., Halliwell B. Blood radicals: reactive nitrogen species, reactive oxygen species, transition metal ions, and the vascular system. Pharm Res. 1996 May;13(5):649–662. doi: 10.1023/a:1016079012214. [DOI] [PubMed] [Google Scholar]
  23. Darzynkiewicz Z., Li X., Gong J. Assays of cell viability: discrimination of cells dying by apoptosis. Methods Cell Biol. 1994;41:15–38. doi: 10.1016/s0091-679x(08)61707-0. [DOI] [PubMed] [Google Scholar]
  24. Devlin R. B. Identification of subpopulations that are sensitive to ozone exposure: use of end points currently available and potential use of laboratory-based end points under development. Environ Health Perspect. 1993 Dec;101 (Suppl 4):225–230. doi: 10.1289/ehp.93101s4225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Enright H., Miller W. J., Hays R., Floyd R. A., Hebbel R. P. Preferential targeting of oxidative base damage to internucleosomal DNA. Carcinogenesis. 1996 May;17(5):1175–1177. doi: 10.1093/carcin/17.5.1175. [DOI] [PubMed] [Google Scholar]
  26. Gold D. R., Allen G., Damokosh A., Serrano P., Hayes C., Castillejos M. Comparison of outdoor and classroom ozone exposures for school children in Mexico City. J Air Waste Manag Assoc. 1996 Apr;46(4):335–342. [PubMed] [Google Scholar]
  27. Grollman A. P., Moriya M. Mutagenesis by 8-oxoguanine: an enemy within. Trends Genet. 1993 Jul;9(7):246–249. doi: 10.1016/0168-9525(93)90089-z. [DOI] [PubMed] [Google Scholar]
  28. Gutteridge J. M. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem. 1995 Dec;41(12 Pt 2):1819–1828. [PubMed] [Google Scholar]
  29. Haegele A. D., Briggs S. P., Thompson H. J. Antioxidant status and dietary lipid unsaturation modulate oxidative DNA damage. Free Radic Biol Med. 1994 Jan;16(1):111–115. doi: 10.1016/0891-5849(94)90247-x. [DOI] [PubMed] [Google Scholar]
  30. Harkema J. R., Plopper C. G., Hyde D. M., St George J. A., Wilson D. W., Dungworth D. L. Response of the macaque nasal epithelium to ambient levels of ozone. A morphologic and morphometric study of the transitional and respiratory epithelium. Am J Pathol. 1987 Jul;128(1):29–44. [PMC free article] [PubMed] [Google Scholar]
  31. Ichinose T., Yajima Y., Nagashima M., Takenoshita S., Nagamachi Y., Sagai M. Lung carcinogenesis and formation of 8-hydroxy-deoxyguanosine in mice by diesel exhaust particles. Carcinogenesis. 1997 Jan;18(1):185–192. doi: 10.1093/carcin/18.1.185. [DOI] [PubMed] [Google Scholar]
  32. Kehrer J. P. Free radicals as mediators of tissue injury and disease. Crit Rev Toxicol. 1993;23(1):21–48. doi: 10.3109/10408449309104073. [DOI] [PubMed] [Google Scholar]
  33. Klaunig J. E., Xu Y., Bachowski S., Ketcham C. A., Isenberg J. S., Kolaja K. L., Baker T. K., Walborg E. F., Jr, Stevenson D. E. Oxidative stress in nongenotoxic carcinogenesis. Toxicol Lett. 1995 Dec;82-83:683–691. doi: 10.1016/0378-4274(95)03514-1. [DOI] [PubMed] [Google Scholar]
  34. Klaunig J. E., Xu Y., Isenberg J. S., Bachowski S., Kolaja K. L., Jiang J., Stevenson D. E., Walborg E. F., Jr The role of oxidative stress in chemical carcinogenesis. Environ Health Perspect. 1998 Feb;106 (Suppl 1):289–295. doi: 10.1289/ehp.98106s1289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Kozumbo W. J., Hanley N. M., Agarwal S., Thomas M. J., Madden M. C. Products of ozonized arachidonic acid potentiate the formation of DNA single strand breaks in cultured human lung cells. Environ Mol Mutagen. 1996;27(3):185–195. doi: 10.1002/(SICI)1098-2280(1996)27:3<185::AID-EM3>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
  36. Kvam E., Tyrrell R. M. Induction of oxidative DNA base damage in human skin cells by UV and near visible radiation. Carcinogenesis. 1997 Dec;18(12):2379–2384. doi: 10.1093/carcin/18.12.2379. [DOI] [PubMed] [Google Scholar]
  37. Lee J. G., Madden M. C., Reed W., Adler K., Devlin R. The use of the single cell gel electrophoresis assay in detecting DNA single strand breaks in lung cells in vitro. Toxicol Appl Pharmacol. 1996 Nov;141(1):195–204. doi: 10.1006/taap.1996.0276. [DOI] [PubMed] [Google Scholar]
  38. Li X. Y., Gilmour P. S., Donaldson K., MacNee W. In vivo and in vitro proinflammatory effects of particulate air pollution (PM10). Environ Health Perspect. 1997 Sep;105 (Suppl 5):1279–1283. doi: 10.1289/ehp.97105s51279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Loft S., Poulsen H. E. Cancer risk and oxidative DNA damage in man. J Mol Med (Berl) 1996 Jun;74(6):297–312. doi: 10.1007/BF00207507. [DOI] [PubMed] [Google Scholar]
  40. Mathison B. H., Harman A. E., Bogdanffy M. S. DNA damage in the nasal passageway: a literature review. Mutat Res. 1997 Oct 31;380(1-2):77–96. doi: 10.1016/s0027-5107(97)00128-0. [DOI] [PubMed] [Google Scholar]
  41. Michaels M. L., Miller J. H. The GO system protects organisms from the mutagenic effect of the spontaneous lesion 8-hydroxyguanine (7,8-dihydro-8-oxoguanine). J Bacteriol. 1992 Oct;174(20):6321–6325. doi: 10.1128/jb.174.20.6321-6325.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Nagashima M., Kasai H., Yokota J., Nagamachi Y., Ichinose T., Sagai M. Formation of an oxidative DNA damage, 8-hydroxydeoxyguanosine, in mouse lung DNA after intratracheal instillation of diesel exhaust particles and effects of high dietary fat and beta-carotene on this process. Carcinogenesis. 1995 Jun;16(6):1441–1445. doi: 10.1093/carcin/16.6.1441. [DOI] [PubMed] [Google Scholar]
  43. Nehls P., Seiler F., Rehn B., Greferath R., Bruch J. Formation and persistence of 8-oxoguanine in rat lung cells as an important determinant for tumor formation following particle exposure. Environ Health Perspect. 1997 Sep;105 (Suppl 5):1291–1296. doi: 10.1289/ehp.97105s51291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Perera F. P., Mooney L. A., Dickey C. P., Santella R. M., Bell D., Blaner W., Tang D., Whyatt R. M. Molecular epidemiology in environmental carcinogenesis. Environ Health Perspect. 1996 May;104 (Suppl 3):441–443. doi: 10.1289/ehp.96104s3441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Poulsen H. E., Prieme H., Loft S. Role of oxidative DNA damage in cancer initiation and promotion. Eur J Cancer Prev. 1998 Feb;7(1):9–16. [PubMed] [Google Scholar]
  46. Priemé H., Loft S., Klarlund M., Grønbaek K., Tønnesen P., Poulsen H. E. Effect of smoking cessation on oxidative DNA modification estimated by 8-oxo-7,8-dihydro-2'-deoxyguanosine excretion. Carcinogenesis. 1998 Feb;19(2):347–351. doi: 10.1093/carcin/19.2.347. [DOI] [PubMed] [Google Scholar]
  47. Randerath K., Zhou G. D., Monk S. A., Randerath E. Enhanced levels in neonatal rat liver of 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-hydroxydeoxyguanosine), a major mutagenic oxidative DNA lesion. Carcinogenesis. 1997 Jul;18(7):1419–1421. doi: 10.1093/carcin/18.7.1419. [DOI] [PubMed] [Google Scholar]
  48. Recio L. Oncogene and tumor suppressor gene alterations in nasal tumors. Mutat Res. 1997 Oct 31;380(1-2):27–31. doi: 10.1016/s0027-5107(97)00124-3. [DOI] [PubMed] [Google Scholar]
  49. Reist M., Jenner P., Halliwell B. Sulphite enhances peroxynitrite-dependent alpha1-antiproteinase inactivation. A mechanism of lung injury by sulphur dioxide? FEBS Lett. 1998 Feb 20;423(2):231–234. doi: 10.1016/s0014-5793(98)00099-4. [DOI] [PubMed] [Google Scholar]
  50. Rochelle L. G., Fischer B. M., Krunkosky T. M., Wright D. T., Adler K. B. Environmental toxins induce intracellular responses of airway epithelium through reactive species of oxygen and nitrogen. Roger S. Mitchell Lecture. Chest. 1996 Mar;109(3 Suppl):35S–39S. doi: 10.1378/chest.109.3_supplement.35s. [DOI] [PubMed] [Google Scholar]
  51. Roldán-Arjona T., Wei Y. F., Carter K. C., Klungland A., Anselmino C., Wang R. P., Augustus M., Lindahl T. Molecular cloning and functional expression of a human cDNA encoding the antimutator enzyme 8-hydroxyguanine-DNA glycosylase. Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8016–8020. doi: 10.1073/pnas.94.15.8016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Singh N. P., McCoy M. T., Tice R. R., Schneider E. L. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res. 1988 Mar;175(1):184–191. doi: 10.1016/0014-4827(88)90265-0. [DOI] [PubMed] [Google Scholar]
  53. Southorn P. A., Powis G. Free radicals in medicine. II. Involvement in human disease. Mayo Clin Proc. 1988 Apr;63(4):390–408. doi: 10.1016/s0025-6196(12)64862-9. [DOI] [PubMed] [Google Scholar]
  54. Spencer J. P., Jenner A., Aruoma O. I., Cross C. E., Wu R., Halliwell B. Oxidative DNA damage in human respiratory tract epithelial cells. Time course in relation to DNA strand breakage. Biochem Biophys Res Commun. 1996 Jul 5;224(1):17–22. doi: 10.1006/bbrc.1996.0977. [DOI] [PubMed] [Google Scholar]
  55. Spencer J. P., Jenner A., Chimel K., Aruoma O. I., Cross C. E., Wu R., Halliwell B. DNA damage in human respiratory tract epithelial cells: damage by gas phase cigarette smoke apparently involves attack by reactive nitrogen species in addition to oxygen radicals. FEBS Lett. 1995 Nov 20;375(3):179–182. doi: 10.1016/0014-5793(95)01199-o. [DOI] [PubMed] [Google Scholar]
  56. Spencer J. P., Jenner A., Chimel K., Aruoma O. I., Cross C. E., Wu R., Halliwell B. DNA strand breakage and base modification induced by hydrogen peroxide treatment of human respiratory tract epithelial cells. FEBS Lett. 1995 Oct 30;374(2):233–236. doi: 10.1016/0014-5793(95)01117-w. [DOI] [PubMed] [Google Scholar]
  57. Steinberg J. J., Gleeson J. L., Gil D. The pathobiology of ozone-induced damage. Arch Environ Health. 1990 Mar-Apr;45(2):80–87. doi: 10.1080/00039896.1990.9935930. [DOI] [PubMed] [Google Scholar]
  58. Tomatis L., Huff J., Hertz-Picciotto I., Sandler D. P., Bucher J., Boffetta P., Axelson O., Blair A., Taylor J., Stayner L. Avoided and avoidable risks of cancer. Carcinogenesis. 1997 Jan;18(1):97–105. doi: 10.1093/carcin/18.1.97. [DOI] [PubMed] [Google Scholar]
  59. Toyokuni S., Sagripanti J. L. Association between 8-hydroxy-2'-deoxyguanosine formation and DNA strand breaks mediated by copper and iron. Free Radic Biol Med. 1996;20(6):859–864. doi: 10.1016/0891-5849(95)02184-1. [DOI] [PubMed] [Google Scholar]
  60. Weitzman S. A., Weitberg A. B., Clark E. P., Stossel T. P. Phagocytes as carcinogens: malignant transformation produced by human neutrophils. Science. 1985 Mar 8;227(4691):1231–1233. doi: 10.1126/science.3975611. [DOI] [PubMed] [Google Scholar]
  61. Wiseman H., Halliwell B. Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer. Biochem J. 1996 Jan 1;313(Pt 1):17–29. doi: 10.1042/bj3130017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Wiseman H., Kaur H., Halliwell B. DNA damage and cancer: measurement and mechanism. Cancer Lett. 1995 Jun 29;93(1):113–120. doi: 10.1016/0304-3835(95)03792-U. [DOI] [PubMed] [Google Scholar]
  63. Wright D. T., Cohn L. A., Li H., Fischer B., Li C. M., Adler K. B. Interactions of oxygen radicals with airway epithelium. Environ Health Perspect. 1994 Dec;102 (Suppl 10):85–90. doi: 10.1289/ehp.94102s1085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Yarborough A., Zhang Y. J., Hsu T. M., Santella R. M. Immunoperoxidase detection of 8-hydroxydeoxyguanosine in aflatoxin B1-treated rat liver and human oral mucosal cells. Cancer Res. 1996 Feb 15;56(4):683–688. [PubMed] [Google Scholar]
  65. Zhao C., Georgellis A., Flato S., Palmberg L., Thunberg E., Hemminki K. DNA adducts in human nasal mucosa and white blood cells from smokers and non-smokers. Carcinogenesis. 1997 Nov;18(11):2205–2208. doi: 10.1093/carcin/18.11.2205. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES