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. 2000 Jun;57(6):370–375. doi: 10.1136/oem.57.6.370

Influence of genetic susceptibility on the urinary excretion of 8-hydroxydeoxyguanosine of firefighters

Y Hong 1, H Park 1, E Ha 1
PMCID: PMC1739964  PMID: 10810125

Abstract

OBJECTIVES—Oxidative DNA damage has been implicated in carcinogenesis. The DNA damage can be assessed from the urinary excretion of the DNA-repair product 8-hydroxydeoxyguanosine (8-OH-dG). The factors were investigated that influenced the excretion of urinary 8-OH-dG in 78 firefighters.
METHODS—53 Out of 78 firefighters were exposed to fire within 5 days of the study and 25 were not. 8-OH-dG was measured by ELISA and the distribution of the genotypes of CYP1A1, CYP2E1, GSTM1, and GSTT1 was measured by polymerase chain reaction.
RESULTS—The homozygous wild type frequencies of CYP1A1 MspI, CYP1A1 ile-val, CYP2E1, GSTM1, and GSTT1 were 31.5%, 56.2%, 60.3%, 50.7%, and 53.4%, respectively. The geometric mean of urinary 8-OH-dG was 14.1 ng/mg creatinine in more active firefighters and 12.3 ng/mg creatinine in non-exposed and less active subjects. Significantly increased concentrations of urinary 8-OH-dG were found to be associated with cigarette smoking, and 14% of the variation of 8-OH-dG was explained by cigarettes smoked per day. The CYP1A1 MspI, CYP1A1 ile-val, GSTM1, and GSTT1 genetic polymorphisms were not found to be significantly associated with the urinary excretion of 8-OH-dG. However, the subjects carrying the CYP2E1 mutant type excreted higher concentrations of 8-OH-dG and there was a marginally significant interaction of GSTT1 with firefighting activity. Multiple regression analysis confirmed that smoking was the strongest predictor of excretion of 8-OH-dG. Age, body mass index, and firefighting activity were not significant predictive factors for urinary 8-OH-dG.
CONCLUSION—Smoking and CYP2E1 gene polymorphism may be important factors in carcinogenesis and the GSTT1 positive genotype may be a genetic susceptibility factor in firefighters who are exposed regularly to various chemical carcinogens.


Keywords: firefighters; 8-hydroxydeoxyguanosine; susceptibility

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Selected References

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  1. Aronson K. J., Tomlinson G. A., Smith L. Mortality among fire fighters in metropolitan Toronto. Am J Ind Med. 1994 Jul;26(1):89–101. doi: 10.1002/ajim.4700260108. [DOI] [PubMed] [Google Scholar]
  2. Beaumont J. J., Chu G. S., Jones J. R., Schenker M. B., Singleton J. A., Piantanida L. G., Reiterman M. An epidemiologic study of cancer and other causes of mortality in San Francisco firefighters. Am J Ind Med. 1991;19(3):357–372. doi: 10.1002/ajim.4700190309. [DOI] [PubMed] [Google Scholar]
  3. Bergtold D. S., Berg C. D., Simic M. G. Urinary biomarkers in radiation therapy of cancer. Adv Exp Med Biol. 1990;264:311–316. doi: 10.1007/978-1-4684-5730-8_49. [DOI] [PubMed] [Google Scholar]
  4. Brandt-Rauf P. W., Fallon L. F., Jr, Tarantini T., Idema C., Andrews L. Health hazards of fire fighters: exposure assessment. Br J Ind Med. 1988 Sep;45(9):606–612. doi: 10.1136/oem.45.9.606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burnett C. A., Halperin W. E., Lalich N. R., Sestito J. P. Mortality among fire fighters: a 27 state survey. Am J Ind Med. 1994 Dec;26(6):831–833. doi: 10.1002/ajim.4700260612. [DOI] [PubMed] [Google Scholar]
  6. Deakin M., Elder J., Hendrickse C., Peckham D., Baldwin D., Pantin C., Wild N., Leopard P., Bell D. A., Jones P. Glutathione S-transferase GSTT1 genotypes and susceptibility to cancer: studies of interactions with GSTM1 in lung, oral, gastric and colorectal cancers. Carcinogenesis. 1996 Apr;17(4):881–884. doi: 10.1093/carcin/17.4.881. [DOI] [PubMed] [Google Scholar]
  7. Elexpuru-Camiruaga J., Buxton N., Kandula V., Dias P. S., Campbell D., McIntosh J., Broome J., Jones P., Inskip A., Alldersea J. Susceptibility to astrocytoma and meningioma: influence of allelism at glutathione S-transferase (GSTT1 and GSTM1) and cytochrome P-450 (CYP2D6) loci. Cancer Res. 1995 Oct 1;55(19):4237–4239. [PubMed] [Google Scholar]
  8. Feuer E., Rosenman K. Mortality in police and firefighters in New Jersey. Am J Ind Med. 1986;9(6):517–527. doi: 10.1002/ajim.4700090603. [DOI] [PubMed] [Google Scholar]
  9. Golden A. L., Markowitz S. B., Landrigan P. J. The risk of cancer in firefighters. Occup Med. 1995 Oct-Dec;10(4):803–820. [PubMed] [Google Scholar]
  10. Golden A. L., Markowitz S. B., Landrigan P. J. The risk of cancer in firefighters. Occup Med. 1995 Oct-Dec;10(4):803–820. [PubMed] [Google Scholar]
  11. Guengerich F. P., Kim D. H., Iwasaki M. Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects. Chem Res Toxicol. 1991 Mar-Apr;4(2):168–179. doi: 10.1021/tx00020a008. [DOI] [PubMed] [Google Scholar]
  12. Hayashi S., Watanabe J., Kawajiri K. Genetic polymorphisms in the 5'-flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene. J Biochem. 1991 Oct;110(4):559–565. doi: 10.1093/oxfordjournals.jbchem.a123619. [DOI] [PubMed] [Google Scholar]
  13. Hayashi S., Watanabe J., Nakachi K., Kawajiri K. Genetic linkage of lung cancer-associated MspI polymorphisms with amino acid replacement in the heme binding region of the human cytochrome P450IA1 gene. J Biochem. 1991 Sep;110(3):407–411. doi: 10.1093/oxfordjournals.jbchem.a123594. [DOI] [PubMed] [Google Scholar]
  14. Heyer N., Weiss N. S., Demers P., Rosenstock L. Cohort mortality study of Seattle fire fighters: 1945-1983. Am J Ind Med. 1990;17(4):493–504. doi: 10.1002/ajim.4700170407. [DOI] [PubMed] [Google Scholar]
  15. Hirvonen A., Pelin K., Tammilehto L., Karjalainen A., Mattson K., Linnainmaa K. Inherited GSTM1 and NAT2 defects as concurrent risk modifiers in asbestos-related human malignant mesothelioma. Cancer Res. 1995 Jul 15;55(14):2981–2983. [PubMed] [Google Scholar]
  16. Hung H. C., Chuang J., Chien Y. C., Chern H. D., Chiang C. P., Kuo Y. S., Hildesheim A., Chen C. J. Genetic polymorphisms of CYP2E1, GSTM1, and GSTT1; environmental factors and risk of oral cancer. Cancer Epidemiol Biomarkers Prev. 1997 Nov;6(11):901–905. [PubMed] [Google Scholar]
  17. Inoue T., Mu Z., Sumikawa K., Adachi K., Okochi T. Effect of physical exercise on the content of 8-hydroxydeoxyguanosine in nuclear DNA prepared from human lymphocytes. Jpn J Cancer Res. 1993 Jul;84(7):720–725. doi: 10.1111/j.1349-7006.1993.tb02035.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kasai H., Crain P. F., Kuchino Y., Nishimura S., Ootsuyama A., Tanooka H. Formation of 8-hydroxyguanine moiety in cellular DNA by agents producing oxygen radicals and evidence for its repair. Carcinogenesis. 1986 Nov;7(11):1849–1851. doi: 10.1093/carcin/7.11.1849. [DOI] [PubMed] [Google Scholar]
  19. Kasai H., Nishimura S., Kurokawa Y., Hayashi Y. Oral administration of the renal carcinogen, potassium bromate, specifically produces 8-hydroxydeoxyguanosine in rat target organ DNA. Carcinogenesis. 1987 Dec;8(12):1959–1961. doi: 10.1093/carcin/8.12.1959. [DOI] [PubMed] [Google Scholar]
  20. Katoh T., Nagata N., Kuroda Y., Itoh H., Kawahara A., Kuroki N., Ookuma R., Bell D. A. Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genetic polymorphism and susceptibility to gastric and colorectal adenocarcinoma. Carcinogenesis. 1996 Sep;17(9):1855–1859. doi: 10.1093/carcin/17.9.1855. [DOI] [PubMed] [Google Scholar]
  21. Kawajiri K., Nakachi K., Imai K., Yoshii A., Shinoda N., Watanabe J. Identification of genetically high risk individuals to lung cancer by DNA polymorphisms of the cytochrome P450IA1 gene. FEBS Lett. 1990 Apr 9;263(1):131–133. doi: 10.1016/0014-5793(90)80721-t. [DOI] [PubMed] [Google Scholar]
  22. Kihara M., Kihara M., Noda K. Lung cancer risk of GSTM1 null genotype is dependent on the extent of tobacco smoke exposure. Carcinogenesis. 1994 Feb;15(2):415–418. doi: 10.1093/carcin/15.2.415. [DOI] [PubMed] [Google Scholar]
  23. Kihara M., Kihara M., Noda K. Risk of smoking for squamous and small cell carcinomas of the lung modulated by combinations of CYP1A1 and GSTM1 gene polymorphisms in a Japanese population. Carcinogenesis. 1995 Oct;16(10):2331–2336. doi: 10.1093/carcin/16.10.2331. [DOI] [PubMed] [Google Scholar]
  24. Kouri R. E., McKinney C. E., Slomiany D. J., Snodgrass D. R., Wray N. P., McLemore T. L. Positive correlation between high aryl hydrocarbon hydroxylase activity and primary lung cancer as analyzed in cryopreserved lymphocytes. Cancer Res. 1982 Dec;42(12):5030–5037. [PubMed] [Google Scholar]
  25. Leanderson P., Tagesson C. Cigarette smoke-induced DNA damage in cultured human lung cells: role of hydroxyl radicals and endonuclease activation. Chem Biol Interact. 1992 Jan;81(1-2):197–208. doi: 10.1016/0009-2797(92)90034-i. [DOI] [PubMed] [Google Scholar]
  26. Leanderson P., Tagesson C. Cigarette smoke-induced DNA-damage: role of hydroquinone and catechol in the formation of the oxidative DNA-adduct, 8-hydroxydeoxyguanosine. Chem Biol Interact. 1990;75(1):71–81. doi: 10.1016/0009-2797(90)90023-g. [DOI] [PubMed] [Google Scholar]
  27. Lees P. S. Combustion products and other firefighter exposures. Occup Med. 1995 Oct-Dec;10(4):691–706. [PubMed] [Google Scholar]
  28. Loft S., Vistisen K., Ewertz M., Tjønneland A., Overvad K., Poulsen H. E. Oxidative DNA damage estimated by 8-hydroxydeoxyguanosine excretion in humans: influence of smoking, gender and body mass index. Carcinogenesis. 1992 Dec;13(12):2241–2247. doi: 10.1093/carcin/13.12.2241. [DOI] [PubMed] [Google Scholar]
  29. Nakachi K., Imai K., Hayashi S., Watanabe J., Kawajiri K. Genetic susceptibility to squamous cell carcinoma of the lung in relation to cigarette smoking dose. Cancer Res. 1991 Oct 1;51(19):5177–5180. [PubMed] [Google Scholar]
  30. Nakajima T., Elovaara E., Anttila S., Hirvonen A., Camus A. M., Hayes J. D., Ketterer B., Vainio H. Expression and polymorphism of glutathione S-transferase in human lungs: risk factors in smoking-related lung cancer. Carcinogenesis. 1995 Apr;16(4):707–711. doi: 10.1093/carcin/16.4.707. [DOI] [PubMed] [Google Scholar]
  31. Sama S. R., Martin T. R., Davis L. K., Kriebel D. Cancer incidence among Massachusetts firefighters, 1982-1986. Am J Ind Med. 1990;18(1):47–54. doi: 10.1002/ajim.4700180106. [DOI] [PubMed] [Google Scholar]
  32. Shigenaga M. K., Gimeno C. J., Ames B. N. Urinary 8-hydroxy-2'-deoxyguanosine as a biological marker of in vivo oxidative DNA damage. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9697–9701. doi: 10.1073/pnas.86.24.9697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Tornling G., Gustavsson P., Hogstedt C. Mortality and cancer incidence in Stockholm fire fighters. Am J Ind Med. 1994 Feb;25(2):219–228. doi: 10.1002/ajim.4700250208. [DOI] [PubMed] [Google Scholar]
  34. Villard P. H., Seree E., Lacarelle B., Therene-Fenoglio M. C., Barra Y., Attolini L., Bruguerole B., Durand A., Catalin J. Effect of cigarette smoke on hepatic and pulmonary cytochromes P450 in mouse: evidence for CYP2E1 induction in lung. Biochem Biophys Res Commun. 1994 Aug 15;202(3):1731–1737. doi: 10.1006/bbrc.1994.2135. [DOI] [PubMed] [Google Scholar]
  35. Yu M. W., Gladek-Yarborough A., Chiamprasert S., Santella R. M., Liaw Y. F., Chen C. J. Cytochrome P450 2E1 and glutathione S-transferase M1 polymorphisms and susceptibility to hepatocellular carcinoma. Gastroenterology. 1995 Oct;109(4):1266–1273. doi: 10.1016/0016-5085(95)90587-1. [DOI] [PubMed] [Google Scholar]

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