The Korean Journal of Pesticide Science (농약과학회지)

The Korean Society of Pesticide Science (한국농약과학회)
권호 표지

Thyroid Hormone-like Activity of Alachlor as R Endocrine Disruptor in Rats and HeLaTRE Cell Culture

랫드와 HeLaTRE Cell에서의 Alachlor에 의한 갑상선 호르몬성 영향 연구

  • You, Are-Sun (Division of Hazardous Substances, Department of Crop Life Safety, National Institute of Agricultural Science & Technology) ;
  • Jeong, Mi-Hye (Division of Hazardous Substances, Department of Crop Life Safety, National Institute of Agricultural Science & Technology) ;
  • Paik, Kyung-Hun (Division of Hazardous Substances, Department of Crop Life Safety, National Institute of Agricultural Science & Technology) ;
  • Kim, Byung-Seok (Division of Hazardous Substances, Department of Crop Life Safety, National Institute of Agricultural Science & Technology) ;
  • Kim, Jin-Bae (Division of Hazardous Substances, Department of Crop Life Safety, National Institute of Agricultural Science & Technology) ;
  • Kwon, Oh-Kyung (Division of Hazardous Substances, Department of Crop Life Safety, National Institute of Agricultural Science & Technology)
  • 유아선 (농업과학기술원 농산물안전성부 유해물질과) ;
  • 정미혜 (농업과학기술원 농산물안전성부 유해물질과) ;
  • 박경훈 (농업과학기술원 농산물안전성부 유해물질과) ;
  • 김병석 (농업과학기술원 농산물안전성부 유해물질과) ;
  • 김진배 (농업과학기술원 농산물안전성부 유해물질과) ;
  • 권오경 (농업과학기술원 농산물안전성부 유해물질과)
  • Published : 2008.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

This study was designed to investigate the suitability of the pubertal assay and the enhanced TG 407 as methods for detection of endocrine-mediated effects, especially thyroid function. Male and female Sprague-Dawley rats were gavaged daily with 0, 12.5, 25, 50 mg/kg alachlor in corn oil during 30 days. The effects of alachlor on thyroid gland, the genital organs and thyroid hormone were measured in male and female rats. Dose of alachlor 25, 50 mg/kg/day increased relative weight of testis and thyroid gland in exposed male rats and decreased relative weight of vagina in exposed female rats. Relative weight of thyroid gland was decreased in alachlor 25 mg/kg/day exposed female rats. Dose of alachlor 25, 50 mg/kg/day decreased plasma T4 and testosterone in female rats. Another purpose of this study was to investigate the effects of endocrine disruptors as like thyroid hormone in vitro. Luciferase activity was measured to dectect reaction of test chemicals and thyroid hormone response elements in HeLaTRE cell. Dose of alachlor 1 nM-1000 nM increased 100-134% luciferase activity compared with control.

내분비장애 추정물질의 분류를 위해 많은 시험법이 연구되고 있는데 추후 내분비장애 추정물질로 분류된 기등록 농약에 대한 자료요구 또는 신규 등록농약에 대한 등록기준의 추가 등을 고려하여 OECD와 EPA에서 권장하는 시험법을 확립하고자 본 연구를 수행하였다. 시험약제를 30일간 경구 투여하여 조사한 결과, alachlor 투여 수컷에서 25 mg/kg/day, 50 mg/kg/day에서 고환과 갑성선의 중량이 증가하였다. Alachlor 투여 암컷에서는 질의 중량이 25, 50 mg/kg/day에서 감소하였고 25 mg/kg/day에서 갑상선의 중량이 감소하였다. Alachlor 투여 암컷 25, 50 mg/kg/day에서 주요 갑상선 호르몬인 T4와 성호르몬 testosterone이 감소하였다. 따라서 pubertal assay 결과 alachlor는 갑상선 호르몬성 영향이 의심되었다. 시험세포를 이용한 시험 결과, 시험약제를 1 nM에서 1000 nM까지 처리하였을 때 음성대조군과 비교하여 alachlor는 100-134%의 갑상선 호르몬성 영향을 나타내었다. 따라서 세포를 이용한 시험에서는 alachlor에 의한 갑상선 호르몬성 영향이 나타나는 것으로 판단되었다. 항갑상선 호르몬성 영향 시험에서는 시험약제 100 nM과 T4의 혼합 처리시 alachlor는 항갑상선 호르몬성 영향은 나타나지 않았다.

Keywords

References

  1. Ashizawa, K. and S. Y. Cheng (1992) Regulation of thyroid hormone receptor-mediated transcription by a cytosol protein, Proc. Natl. Acad. Sci. USA 89, 9277/9281
  2. Brucker-Davis, F. (1998) Effects of environmental synthetic chemicals on thyroid function, Thyroid 8, 827/856
  3. Caroline, S. Kim, Fumihiko, Furuya, Hao, Ying, Yasuhito, Kato, John, A. Hanover and Sheue-yann Cheung (2007) Gelsolin: A Novel Thyroid hormone Receptor-$\beta$ Interacting Protein that Modulates Tumor Progression in a Mouse Model of Follicular Thyroid Cancer, Endocrinology 148(3):1306-1312 https://doi.org/10.1210/en.2006-0923
  4. Chung, J. H. (2006) From A to Z of Thyroid Disease with Which the Psychiatrist should be Familiar, Korean J Psychosomatic Medicine, 14(2):73-80
  5. Dearfield, K. L., N. E. McCarroll, A. Protzel, H. F. Stack, M. A. Jackson and M. D. Waters (1999) A survey of EPA/OPP and openm literature on selected pesticide chemicals II. Mutagenicity and carcinogenicity of selected chloracetanilides and related compounds. Mutat Res, 443, 183-221 https://doi.org/10.1016/S1383-5742(99)00019-8
  6. DeVito, M., L. Biegel, A. Brouwer, S. Brown, F. Brucker-Davis, A. O. Cheek, R. Christensen, T. Colborn, P. Cooke, J. Crissman, K. Crofton, D. Doerge, E. Gray, P. Hauser, P. Hurley, M. Kohn, J. Lazar, S. McMaster, M. McClain, E. McConnell, C. Meier, R. Miller, J. Tietge and R. Tyl (1999) Screening methods for thyroid hormone disruptors, Environ. Health Perspect. 107, 407/415
  7. Ekins, R., P. Edwards and B. Newman (1982) The role of binding proteins in hormone delivery. In: Albertini, A., Ekins, R. P. (Eds.), Free Hormones in Blood. Elsevier, New York, pp. 3/44
  8. Galassie, S., A. Provini, S. Mangiapan and E. Benfenati (1996) Alachlor and its metabolites in surface water, Chemosphere, 32(2):229-237 https://doi.org/10.1016/0045-6535(95)00335-5
  9. Hadley, M. E. (1996) Endocrinology, 4th ed. Prentice Hall, New Jersey, pp. 290/313
  10. Hennemann, G., R. Docter, E. C. Friesema, M. de Jong, E. P. Krenning and T. J. Visser (2001) Plasma membrane transport of thyroid hormones and its role in thyroid hormone metabolism and bioavailability, Endocr. Rev. 22, 451/476
  11. Hong, S. W. (2000) Radioiodine therapy for differentiated thyroid cancer, Korean J Nucl Med, 34, 265-275
  12. Kashian, D. R. and S. I. Dodson (2002) Effects of common-use pesticides on developmental and reproductive processes in Daphnia, Toxicol Ind Health. 18(5):225-35 https://doi.org/10.1191/0748233702th146oa
  13. Kim, Y. S. and K. S. Kim (2001) Clincal study of 1 case of patient with Hypothyroidism, Korean J oriental medical prescription Vol. 9(1), 397-403
  14. Lazar, M. A. (1993) Thyroid hormone receptors: multiple forms, multiple possibilities, Endocr. Rev. 14, 184-193
  15. Lee, J. R., B. C. Ahn, S. Y. Jeong, Jaetae Lee, K. B. Lee (2003) Detection for Residual Thyroid Tissue and Metastatic Lesion after Total Thyroidectomy in Patients with Differentiated Thyroid Cancer: Comparison between Tc-00m Pertechnetate Scan and High Dose I-131 Therapy Scan, Korean J Nucl Med : Vol. 37(2), 120-127
  16. Marty, M. S., J. W. Crissman and E. W. Carney (2002) Evaluation of the Male Pubertal Assay's Ability to Detect Thyroid Inhibitor and Dopaminergic Agents, Toxicological sciences 60, 63-76 https://doi.org/10.1093/toxsci/60.1.63
  17. McKenna, N. J., R. B. Lanz and B. W. O'Malley (1999) Nuclear receptor coregulators: cellular and molecular biology, Endocr. Rev. 20, 331/344
  18. Mendel, C. M. (1989) The free hormone hypothesis: a physiologically based mathematical model, Endocr. Rev. 10, 232/274
  19. Miyazaki, K., T. Iwasaki, A. Takeshita, Y. Kuroda and N. Koibuchi (2004) Polychlorinated biphenyls suppress thyroid hormone receptor-mediated transcription through a novel mechanism, J Biol Chem, 279, 18195-18202 https://doi.org/10.1074/jbc.M310531200
  20. Mori, J., S. Suzuki, M. Kobayashi, T. Inagaki, A. Komatsu, T. Takeda, T. Miyamoto, K. Ichikawa and K. Hashizume (2002), Nicotinamide adenine dinucleotide phosphate-dependent cytosolic T3 binding protein as a regulator for T3-mediated transactivation, Endocrinology 143, 1538/1544
  21. Naciff, J. M. and G. P. Daston (2004) Toxicogenomic approach to endocrine disruptors: identification of a transcript profile charateristic of chemicals with estrogenic activity, Toxicol Pathol, 32 Supple 2, 59-70 https://doi.org/10.1080/01926230490463812
  22. Nagel, S. C., F. S. vom Saal, K. A. Thayer, M. G. Dhar, M. Boechler and W. V. Welshons (1997) Relative binding affinity-serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol A and octylphenol. Environ, Health Perspect. 105, 70/76
  23. Nagel, S. C., F. S. vom Saal and W. V. Welshons (1998) The effective free fraction of estradiol and xenoestrogens in human serum measured by whole cell uptake assays: physiology of delivery modifies estrogenic activity, Proc. Soc. Exp. Biol. Med. 217, 300/309
  24. Osano, O., W. Admiral, H. J. Klamer, D. Pastor and E. A. Bleeker (2002) Comparatove toxic and genotoxic effects of chloroacetanilides, formamidones and their degradation products on Vibrio fisheri and Chironomus riparius, Environmental Pollution, 119, 195-202 https://doi.org/10.1016/S0269-7491(01)00334-7
  25. Robbins, J. (1996) Thyroid hormone transport proteins and the physiology of hormone binding. In: Braverman, L.E., Utiger, R.D. (Eds.), Weiner and Ingbar's The Thyroid, 7th ed.. Lippincott-Raven, Philadelphia, PA, pp. 96/110
  26. Scotte, C, L. Siming, L. Russell, H. Ernest and L. Randy (1999) In vitro metabolism of alachlor by human liver microsomes and human cytochrome P450 isoforms, Chemico-Biological Interactions, 122(1), 27-39 https://doi.org/10.1016/S0009-2797(99)00107-6
  27. Sheman, S. I. (2002) Management of differentiated thyroid carcinoma, Korean J Endocrinol 17(Supp-2):31-51
  28. Shupnik, M. A., E. C. Rdgway, W. W. Chin (1994) Throtropin Mol. Biol.: Update Endo. Rev (Monograph) 3, 18-22
  29. St. Germain, D. L. (1994) Iodothyronine deiodinases. Trends Endocrinol. Metab. 5, 36/42
  30. Stoker, T. E., L. G. Parks, L. E. Gray and R. L. Cooper (2000) Endocrine-disrupting chemicals: prepubertal exposures and effects on sexual maturation and thyroid function in the male rat. A focus on the EDSTAC recommendations, Endocrine Disrupter Screening and Testing Advisory Commottee, Crit Rev Toxicol, 30, 197-252 https://doi.org/10.1080/10408440091159194
  31. Tessier, D. M. and J. M. Clark (1998), An enzyme immunoassay for mutagenic metabolites of the herbicide alachlor, Analytica Chimica Acta 376, 103-112 https://doi.org/10.1016/S0003-2670(98)00442-5
  32. United States Environmental Prtectopm Agency Office of Pesticides Programs (1985) Special review of certain pesticide products. Alachlor: Position document 1. PB85-175503
  33. World Wildlife Fund Canada (1996) http://www.wwfcanada.org
  34. Yamasaki, K., Y. Tago, K. Nagai, M. Sawaki, S. Noda and M. Takatsuki (2002) Comparison of toxicity studies based on the draft protocol for the 'Enhanced OECD Test Guideline no. 407' and the research protocol of 'Pubertal Development and Thyroid Function in Immature Male Rats' with 6-n- propyl-2-thiouracil, Arch Toxicol 76:495-501 https://doi.org/10.1007/s00204-002-0371-5
  35. Yen, P. M. and W. W. Chin (1994) New advances in understanding the molecular mechanisms of thyroid hormone action, Trends Endocrinol. Metab. 5, 65/72
  36. Yu, C. J., W. J. Ahn, H. Y. Lee and H. K. Ro (1986) The clinical Study on 39 Cases of Subclinical Hypothyroidism, Korean J Nucl Med, 20(1), 67-73
  37. 枓鎬京 (1993) 동의현계학, 서울, 동양의학연구소 1059-1065
  38. 서울대학교 의과대학 생리학교실 (1996), 생리학, 서울, 의학문화사, 373
  39. 전국의과대학교수 번역 (1999) 오늘의 진단과 치료, 서울, 한우리 1187-1188
  40. 정상희, 김병용, 구현옥, 박종명, 정갑수, 조준형 (2002) 화학물질의 갑상선호르몬계 교란유발성 고감도 간이 검색기법 개발, 국립수의과학연구보고서 79-87
  41. 해리슨 내과학 (1997) 서울, 정담출판사 2089
  42. 홍사석 (1993) 이우주의 약리학강의, 서울, 의학문화사 503-504