대한임상독성학회지 (Journal of The Korean Society of Clinical Toxicology)

  • 제14권2호
  • /
  • Pages.144-150
  • /
  • 2016
  • /
  • 1738-1320(pISSN)
  • /
  • 2508-6332(eISSN)
대한임상독성학회 (Korean society of Clincal Toxicology)
권호 표지
DOI QR코드

DOI QR Code

글라이포세이트의 유전자 독성에 대한 멜라토닌의 유전자 보호 효과

Genoprotective Effect of Melatonin Against to the Genotoxicity of Glyphosate on Human Blood Lymphocytes

  • 김정규 (계명대학교 의과대학 동산의료원 응급의학교실) ;
  • 최우익 (계명대학교 의과대학 동산의료원 응급의학교실) ;
  • 이재호 (계명대학교 의과대학 해부학교실) ;
  • 최인장 (계명대학교 의과대학 해부학교실) ;
  • 진상찬 (계명대학교 의과대학 동산의료원 응급의학교실)
  • Kim, Jung-Gyu (Department of Emergency Medicine, School of Medicine, Keimyung University, Dongsan Medical Center) ;
  • Choi, Woo-Ik (Department of Emergency Medicine, School of Medicine, Keimyung University, Dongsan Medical Center) ;
  • Lee, Jae-Ho (Department of Anatomy, College of Medicine, Keimyung University) ;
  • Choi, In-Jang (Department of Anatomy, College of Medicine, Keimyung University) ;
  • Jin, Sang-Chan (Department of Emergency Medicine, School of Medicine, Keimyung University, Dongsan Medical Center)
  • 투고 : 2016.09.22
  • 심사 : 2016.10.11
  • 발행 : 2016.12.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Purpose: Glyphosate is a widely used non-selective herbicide. Previous studies have shown that glyphosate has genotoxicity, and that even low-doses of glyphosate can cause DNA damage. Melatonin is a hormone produced and secreted by the pineal gland that is known to be a potent anti-carcinogen, anti-oxidant, and genetic protector. This study was conducted to investigate the genoprotective effect of melatonin against glyphosate in human blood lymphocytes. Methods: Human peripheral blood was obtained from 15 young, healthy volunteers and cultured under four different toxicologic conditions. The four groups consisted of a control group, glyphosate only group (300 ng/mL), glyphosate with low level of melatonin group ($50{\mu}M$), and glyphosate with high level of melatonin group ($200{\mu}M$). The mean Sister Chromatid Exchange (SCE) frequency of each group was then analyzed. Results: Glyphosate exposed groups had a higher mean SCE frequency ($10.33{\pm}2.50$) than the control group ($6.78{\pm}2.31$, p<0.001). Interestingly, the group that received a low-level of melatonin had a lower mean SCE frequency ($8.67{\pm}2.58$) than the glyphosate-only group, while the group that received a high level of melatonin had a much lower mean SCE frequency ($8.06{\pm}2.50$) than the glyphosate-only group. There was statistical significance. Conclusion: Melatonin exerted a potent gene protective effect against the genotoxicity of glyphosate on human blood lymphocytes in a dose-dependent fashion.

키워드

참고문헌

  1. Williams GM, Kroes R, Munro IC. Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans. Regul Toxicol Pharmacol 2000;31:117-65. https://doi.org/10.1006/rtph.1999.1371
  2. Talbot AR, Shiaw M-H, Huang J-S, Yang S-F, Goo T-S, Wang S-H, et al. Acute poisoning with a glyphosate-surfactant herbicide ('Roundup'): a review of 93 cases. Hum Exp Toxicol 1991;10:1-8. https://doi.org/10.1177/096032719101000101
  3. Richard S, Moslemi S, Sipahutar H, Benachour N, Seralini GE. Differential effects of glyphosate and roundup on human placental cells and aromatase. Environ Health Perspect 2005;113:716-20. https://doi.org/10.1289/ehp.7728
  4. Koller VJ, Furhacker M, Nersesyan A, Misik M, Eisenbauer M, Knasmueller S. Cytotoxic and DNA-damaging properties of glyphosate and Roundup in humanderived buccal epithelial cells. Arch Toxicol 2012;86:805-13. https://doi.org/10.1007/s00204-012-0804-8
  5. Lee SH, Kim SJ, Choi WI, Jin SC, Choi IJ, Lee JH. Genotoxicity of low-dose Glyphosate by Sister Chromatid Exchange. J Korean Soc Clin Toxicol 2014;12:8-13.
  6. De Roos AJ, Blair A, Rusiecki JA, Hoppin JA, Svec M, Dosemeci M, et al. Cancer incidence among glyphosateexposed pesticide applicators in the Agricultural Health Study. Environ Health Perspect 2005;113:49-54. https://doi.org/10.1289/ehp.7340
  7. Bolognesi C, Carrasquilla G, Volpi S, Solomon KR, Marshall EJ. Biomonitoring of genotoxic risk in agricultural workers from five colombian regions: association to occupational exposure to glyphosate. J Toxicol Environ Health A 2009;72:986-97. https://doi.org/10.1080/15287390902929741
  8. Schinasi L, Leon ME. Non-Hodgkin lymphoma and occupational exposure to agricultural pesticide chemical groups and active ingredients: a systematic review and metaanalysis. Int J Environ Res Public Health 2014;11:4449-527. https://doi.org/10.3390/ijerph110404449
  9. Reiter RJ. The melatonin rhythm: both a clock and a calendar. Experientia 1993;49:654-64. https://doi.org/10.1007/BF01923947
  10. Hardeland R, Pandi-Perumal SR, Cardinali DP. Melatonin. Int J Biochem Cell Biol 2006;38:313-6. https://doi.org/10.1016/j.biocel.2005.08.020
  11. Barlow-Walden LR, Reiter RJ, Abe M, Pablos M, Menendez-Pelaez A, Chen LD, et al. Melatonin stimulates brain glutathione peroxidase activity. Neurochem Int 1995;26:497-502. https://doi.org/10.1016/0197-0186(94)00154-M
  12. Tan D, Reiter RJ, Manchester LC, Yan M, El-Sawi M, Sainz RM, et al. Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger. Curr Top Med Chem 2002;2:181-97. https://doi.org/10.2174/1568026023394443
  13. Cos S, Sanchez-Barcelo EJ. Melatonin and mammary pathological growth. Front Neuroendocrinol 2000;21:133-70. https://doi.org/10.1006/frne.1999.0194
  14. Anisimov VN, Zabezhinski MA, Popovich IG, Zaripova EA, Musatov SA, Andre V, et al. Inhibitory effect of melatonin on 7, 12-dimethylbenz[a]anthracene-induced carcinogenesis of the uterine cervix and vagina in mice and mutagenesis in vitro. Cancer Lett 2000;156:199-205. https://doi.org/10.1016/S0304-3835(00)00463-8
  15. Anisimov VN. Melatonin and colon carcinogenesis. In: Bartsch C, Bartsch H, Blask DE, Cardinali DP, Hrushesky WJM, Mecke D, editors. The Pineal Gland and Cancer. Heidelberg:Springer:2001. p.240-58.
  16. Cos S, Fern R, Mediavilla M. Melatonin and mammary cancer: a short review. Endocr Relat Cancer 2003;10:153-9.
  17. Subramanian P, Mirunalini S, Dakshayani KB, Pandi-Perumal SR, Trakht I, Cardinali DP. Prevention by melatonin of hepatocarcinogenesis in rats injected with Nnitrosodiethylamine. J Pineal Res 2007;43:305-12. https://doi.org/10.1111/j.1600-079X.2007.00478.x
  18. Mills E, Wu P, Seely D, Guyatt G. Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis. J Pineal Res 2005;39:360-6. https://doi.org/10.1111/j.1600-079X.2005.00258.x
  19. Vijayalaxmi, Reiter RJ, Herman TS, Meltz ML. Melatonin reduces gamma radiation-induced primary DNA damage in human blood lymphocytes. Mutat Res 1998;397:203-8. https://doi.org/10.1016/S0027-5107(97)00211-X
  20. Lee JH, Eom KS, Song DK, Suh SI, Kim DK. In vitro and in vivo effects of melatonin on sister chromatid exchange in human blood lymphocytes exposed to hypoxia. Drug Chem Toxicol 2015:1-4.
  21. Anisimov VN, Popovich IG, Zabezhinski MA, Anisimov SV, Vesnushkin GM, Vinogradova IA. Melatonin as antioxidant, geroprotector and anticarcinogen. Biochim Biophys Acta 2006;1757:573-89. https://doi.org/10.1016/j.bbabio.2006.03.012
  22. Sarto F, Faccioli MC, Cominato I, Levis AG. Aging and smoking increase the frequency of sister-chromatid exchanges (SCE) in man. Mutat Res 1985;144:183-7. https://doi.org/10.1016/0165-7992(85)90137-X
  23. Hirsch BA, Sentz KK, McGue M. Genetic and environmental influences on baseline SCE. Environ Mol Mutagen 1992;20:2-11. https://doi.org/10.1002/em.2850200103
  24. Wilson DM, 3rd, Thompson LH. Molecular mechanisms of sister-chromatid exchange. Mutat Res 2007;616:11-23. https://doi.org/10.1016/j.mrfmmm.2006.11.017
  25. Stults DM, Killen MW, Pierce AJ. The sister chromatid exchange (SCE) assay. Methods Mol Biol 2014;1105:439-55.
  26. Tucker JD, Auletta A, Cimino MC, Dearfield KL, Jacobson-Kram D, Tice RR, et al. Sister-chromatid exchange: second report of the Gene-Tox Program. Mutat Res 1993;297:101-80. https://doi.org/10.1016/0165-1110(93)90001-4
  27. Hagmar L, Bonassi S, Stromberg U, Brogger A, Knudsen LE, Norppa H, et al. Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH). Cancer Res 1998;58:4117-21.
  28. Mourelatos D. Sister chromatid exchange assay as a predictor of tumor chemoresponse. Mutat Res Genet Toxicol Environ Mutagen 2016;803-804:1-12. https://doi.org/10.1016/j.mrgentox.2016.03.011
  29. Galley HF, Lowes DA, Allen L, Cameron G, Aucott LS, Webster NR. Melatonin as a potential therapy for sepsis: a phase I dose escalation study and an ex vivo whole blood model under conditions of sepsis. J Pineal Res 2014;56:427-38. https://doi.org/10.1111/jpi.12134
  30. Shokouhi G, Tubbs RS, Shoja MM, Hadidchi S, Ghorbanihaghjo A, Roshangar L, et al. Neuroprotective effects of high-dose vs low-dose melatonin after blunt sciatic nerve injury. Childs Nerv Syst 2008;24:111-7.