Please use this identifier to cite or link to this item:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37348
Full metadata record
???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
---|---|---|
dc.contributor.advisor | 翁祖輝(Tzuu-Huei Ueng) | |
dc.contributor.author | Chen-Ping Chou | en |
dc.contributor.author | 周正平 | zh_TW |
dc.date.accessioned | 2021-06-13T15:25:09Z | - |
dc.date.available | 2008-09-11 | |
dc.date.copyright | 2008-09-11 | |
dc.date.issued | 2008 | |
dc.date.submitted | 2008-07-21 | |
dc.identifier.citation | Abel, E. L., Lyon, R. P., Bammler, T. K., Verlinde, C. L., Lau, S. S., Monks, T. J., and Eaton, D. L. (2004) Estradiol metabolites as isoform-specific inhibitors of human glutathione S-transferases. Chem. Biol. Interact. 151:21-32.
AboKhatwe, N., and Hollingworth, R. M. (1974) Pesticide chemical affecting some energy-linked fractions in rat liver mitochondria in vivo mice. Toxicol. Appl. Pharmacol. 93:319-328. Abu-Basha, E. B., Sirintorn, Y. A. David, L. H., and Walter, H. H. (1999) Effects of the pesticide amitraz and pancreas: involvement of α2-adrenergic receptors. Metabolism 48:1461-1469. Adlei, A. A., and Weinshilboun, R. M. (2002) Catecholestrogen Sulfation: Possible role in carcinogenesis. Biochem. Biophys. res. Commun. 292: 402-408. Al-Thani, R. K., Al Thani, A. S., Elbetieha, A., and Darmani, H. (2003) Assessment of reproductive and fertility effects of amitraz pesticide in male mice. Toxicol. Lett. 138:253-260. Altobelli, D., Martire M., Maurizi, S., and Preziosi, P. (2001) Interaction of formamidine Pesticides with the Presynaptic α2-adrenoceptor regulating [3H] noradrenaline release from rat hypothalamic synaptosomes, Toxicol. Appl. Pharmacol. 172:179-185. Alvares, A. P. and Mannering, G. J. (1970) Two substrate kinetics of drug-metabolizing enzyme systems of hepatic microsomes. Mol. Pharmacol. 6:206-212. Andres, H. H., Klem, A. I. Szaba, S. M. and Weber, W. W. (1985) New spectrophotometric and radiochemical assays for acetyl-COA: Arylamine N-acetyltransferase applicable to a variety of arylamines. Anal. Biochem. 145:367-375. Arlotto M.P., Trant J.M., and Estabrook R.W. (1991) Measurement of steroid hydroxylation reactions by high-performance liquid chromatography as indicator of P450 identity and function. Methods Enzymol. 206:454-462. B’elanger, A., Pelletier, G., Labrie, F., Barbier, O. and Chouinard, S. (2003) Inactivation of androgens by UDP-glucuronosyl transferase enzymes in humans. TRENDS in Endocrinol. Metab. 14: 473-479. Balizs, G.., and Hewitt, A. (2003) Determination of veterinary drug residues by liquid chromatography and tandem mass spectrometry. Anal. Chim. Acta. 492:105-131. Ball, P., Emons, G., Klingebiel, T., Gruhn, K. M., and Knuppen, R. (1981) Effects of catecholestrogens on luteinizing hormone levels in long term ovariectomized adult rats. Endocrinology 109:1037-1039. Belanger, A., Hum, D. W., Beaulieu, M., Levesque, E., Fuillemette, C., Tchernof, A., Belanger, G., Turgeon, D., and Dubois, S. (1998) Characterization and regulation of UDP-glucuronosyltransferases in steroid target tissue. J. Steroid Biochem. Mol. Biol. 65:301-310. Berlin, A., Yodaiken, R. E., and Henman, B. A. (Eds.) (1984) Assessment of Toxic Agents at the Workplace:Role of Ambient and Biological Monitoring. Martinus Nijhoff Publishers, The Hague, The Netherlands, P. 634. Billich, A., Nussbaumer, P., and Lehr, P. (2000) Stimulation of MCF-7 breast cancer cell proliferation by estrone sulfate and dehydroepiandrosterone sulfate: inhibition by novel non-steroidal steroid sulfatase inhibitors. J. Steroid Biochem. Mol. Biol. 73:225-235. Brady, S. S. (1992) At-harvest residues of amitraz in or on pears resulting from two applications of MITAC EC or MITAC WP using both a 14-day and a 30-day intercal between applications USA and Cannada. NOR-AM. Laboratory Prozeit L-91R-01. NOR-AM chemical company residue chemistry department Route 2. County Road 1324 Pikeville, NC 27863 (919) 580-3000. Brake, P. B., Christsou, M., Savasű, Bhattacharyya, K., Alesander, D., Larsen, M., and Jefcoate, R. (1995) Selective expression and hormoual regulation of cytochrome P450 1B1 in mammary cells. Proc. Am. Ass. Cancer Res. 36:251. Breaer, H., and Kőster, G. (1974) Interaction between estrogens and neurotransmitters at the hypophysial-hypothalamic level. J. Steroid Biochem. 5: 961-967. Campbell, J. K., and Needham, D. (1984) The metabolism of 「C14」-amitraz by male and female rats. Schering registration document. Campbell, M. A., Gyorkos, J., Leece, B., Homonko, K., and Safe, S. (1983). The effects of twenty-two organochlorine pesticides as inducers of the hepatic drug-metabolizing enzymes. Gen. Pharmac. 14: 445-454. Cannon, S. B., Veazey JM. Jr., Jackson, R. S., Burse, V. W., Hayes, C., Straub, W. E., Landrigan, P. J., and Liddle, J. A. (1978) Epidemic kepone poisoning in chemical workers. Am. J. Epidemiol. 107(6):529-537. Castracane, V. D., and Jordan, V. C. (1975) The effect of estrogen and progesterone on uterine prostaglandin biosynthesis in the ovariectomized rat. Biol. Reprod. 13: 587-596. Chen, T. S., and Hsu, W. H. (1994) Inhibition of insulin release by a formamidine pesticide amitraz and its metabolites in a rat Beta-cell line:An action mediated by Alpha-2 adrenpceptors, a GTP-binding protein and a decrease in cyclic AMP. J. Pharmacol. Exp. Ther. 271:1240-1245. Chou, C. P., Li, H. P., Wang, S. S., and Li, G.. C. (2004) Solid-phase extraction and GC-MSD determination of amitraz and metabolites in urine. J. Food. Drug. Ana. 12(3): 212-216. Chung, W. G.., and Cha, Y. N. (1997) Oxidation of caffeine to theobromine and theophylline is catalyzed primarily by flavin-containing minooxygenase in liver microsomes. Biochem. Biophys. Res. Commum. 235:685-688. Colborn, T., Vom Saal, F. S., and Soto, A. M. (1993) Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environ. Health Perspect. 101: 378-384. Cooper, C. L., Cooper, R., and Faragher, E. B. (1989) Incidence and Perception of psychosocial stress:the relationship with breast cancer. Psychol. Med. 19:415-422. Cooper, R. L., Goldman, J. M., and Stoker, T. (1999) Neuroendocrine and reproductive effects of contemporary-Use pesticides. Toxicol. Ind. Health 15:26-36. Costa, L. G., Gastel, J., and Murphy, S. D. (1991) The formamidine pesticides chlordimeform and amitraz decrease hepatic glutathione in mice through an interaction with Alpha2-adrenoceptors. J. Toxicol. Environ. Health 33:349-358. Costa, L. G., Olibet, G., and Murphy, S. M. (1988) α2-Adrenoceptors as a target for formamidine pesticides : In vitro and in vivo studies in mice. Toxicol. Appl. Pharmacol. 93:318-328. Couch, M., Muller, J, Perry, Y. S., and Winter, J. D. S. (1987) Kinetic analysis of inhibition of human adrenal steroidogenesis by ketoconzole. J. Clin. Endocrinol. Metab. 65: 551-554. Daeseleire, E., Vandeputte, R., and Peteghem, C. V. (1998) Validation of multi-residue methods for the detection of anabolic steroids by GC-MS in muscle tissues and urine samples from cattle. Analyst 123: 2595-2598. Dannan, G. A., Porubek, D. J., Nelson, S. D., Waxman, D. J., and Guengerich, F. P. (1986) 17β-Estradiol 2-and 4-hydroxylation catalyzed by rat hepatic cytochrome P-450: roles of individual forms, inductive effects, developmental patterns, and alterations by gonadectomy and homone veplacement. Endocrinology 118:1952-1960. Davis, J. K., Brownson, R. C., and Garcia, R. (1992) Family pesticide use in the home, garden, orchard, and yard. Arch. Eniviron. Contam. Toxicol. 22:260-266. Demyan, W. F., Song, C. S., Kim, D. S. Her. S., Gallwitz, W., Rao, T. R., Slomczynska, M., Chatterjee, B., and Roy, A. K. (1992) Estrogen sulfotransferase of the rat liver:complementary DNA cloning and age-and sex-specifc regulation of messenger RNA. Mol. Endocrinol. 6: 589-597. Di Mattina, M., Maronian, N., Ashby, H., Loriaux, D. L., and Alberson, B. D. (1988) Ketoconazole inhibits multiple steroidogeuic enzymes involved in androgen biosynthesis in the human ovary. Fertil. Steril. 49:62-65. USEPA. (1996) Amitraz R. E. D. Facts. Prevention, Pesticides and toxic substances USEPA-738-F-96-031. Eroschenko, V. P. and Hackmann, N. L. (1981) Continuous ingestion of different chlordecone (kepone) concentrations and changes in quail reproduction. Toxicol. Environ. Health 8: 659-665. Falany, J. L., Krasnykn, v., Mikheeva, G., and Falany, C. N. (1995) Isolation and expression of an isoform of rat estrogen sulfotransferase. J. Steroid Biochem. Mol. Biol. 52:35-44. Faragher, E. B., and Cooper, C. L. (1990) Type A Stress prone behavior and breast cancer. Psychol. Med. 20:663-670. Fishman, J. (1981). Biological action of catecholestrogens. J. Endocr. 85:59-65. Forsen, A. (1991) Psychosocial stress as a risk for breast cancer. J. Steroid Biochem. 15:111-124. Fotsis, T., Zhang, Y., Pepper, M. S., Adlercreutz, H., Montesano, R., Nawroth, P. P., and Schwelgerer, L. (1994) The endogenous oestrogen metabolite 2-meyhoxyoestradiol inhibits angiogenesis and suppresses tumor growth. Nature 368: 237-239. George, J. E., Davey, R. B., Ahrens, E. H., Pound, J. M., and Drummond, R. O. (1998) Efficacy of amitraz as a dip for the control of Boophilis micrplus(canestrini)(Acari:Ixodidae)on catele. Preven. Veter. Med. 37:55-67. Ghraf, R., and Hiemke, C. H. (1983) Interaction of catechol estrogens with catecholamine synthesis and metabolism. In Merrian, G. R. and Lipsett, M. B. (eds) Catechol Estrogens. Raven Press, New York. 177-187. Goldman, J. M., Cooper, R. L., Laws, S. C., Rehnberg, G. L., Edwards, T. L., McElroy, W. K., and Hein, J. F. (1990) Chlordimeform induced alterations in endocrine regulation within the male rat reproductive system. Toxicol. Appl. Pharmacol. 104:25-35. Goldman, J. M., Cooper, R. L., Rehnberg, G. L., Edwards, T. L., McElroy, W. K., and Hein, J. (1991) Suppression of the luteinizing hormone surge by chlordimeform in ovariectomized, steroid-primed female rats. Pharmacol. Toxicol. 68, 131-136. Gonzalo-Lumbreras, R.,and Izquierdo-Hornillos, R. (2000) Optimization of the high-performance liquid chromatographic separation of a complex mixture containing urinary steroids, boldenone and bolasterone: application to urine samples. J. Chromatogr. B 742:47-57. Gonzalo-Lumbreras, R., Muňiz-Valencia, R., Santos-Montes, A., and Izquierdo-Hornillos, R. (2007) Liquid chromatographic method development for sterojds determination (corticoids and anabolics) application to animal feed samples. J. Chromatogr. A 1156:321-330. Guengerich, F. P. (1988) Oxidation of 17α-ethynylestradiol by human liver cytochrome P-450. Mol. Pharmacol. 33:500-508. Guillette, L. J., Gross, IS., Masson, G. R., Matter, J. M., Percival, H. F., and Woodward, A. R. (1994) Developmental abnormalities of the gonad and abnormal sex hormone concentrations on juvenile alligators from contaminated and control lakes in Florida. Environ. Health Perspect. 102:680-688. Haake, J., Kelly, M., Keys, B., and Safe, S. (1987) The effects of organochlorine pesticides as inducers of testosterone and benzo[a]pyrene hydroxylase. Gen. Pharmacol. 18:165-169. Hartmann, S. and Steinhart, H. (1997) Simultaneous determination of anabolic and catabolic steroid hormones in meat by gas chromatography-mass spectrometry. J. Chromatogr. B 704:105-117. Hayes, C. L., Spink, D. C., Spink, B. C., Cao, J. Q., Walker, N. J., and Sutter, T. R. (1996) 17β-Estradiol hydroxylation catalyzed by human cytochrome P450 1B1. Proc. Natl. Acad. Sci. USA. 93:9776-9781. Heckman, W. R., Kane, B. R., Pakyz, R. E., and Consentino, J. (1992) The effect of ketoconazole on endocrine and reproductive parameters in male mice and rats. J. Androl. 13:191-198. Hollingworth, R. M., Leister, J., and Ghali, G. (1979) Mode of action of formamidine Pesticides : An evaluation of monoamine oxidase as the target. Chem. Biol. Interact. 24:35-49. Impens, S., Courtheyn, D., Wasch, K., and Brabander, H. F. (2003) Faster analysis of anabolic steroids in kidney fat by downscaling the sample size and using gas chromatography-tandem mass spectrometry. Anal. Chim. Acta 483: 269-280. Khan, J. A., Reddy, B. V., Mahboob, M., Rahman, M. F., and Jamil, K. (2001) Effect of phosphorothionate on the reproductive system of male rats. J. Environ. Sci. Health. B 36: 445-456. King, D. D., Rios, G. R., Green, M. D., and Tephly, T. R. (2000) UDP-glucuronosyltransferases. Curr. Drug Metab. 1: 143-161. Levesque, E., Beaulieu, M., Guillemette, C., Hum, D. W., and Belanger, A. (1998) Effect of fibroblastic growth factors (FGF) on steroid UDP-glucuronosyltransferase expression and activity in the LNCaP cell line. J. Steroid Biochem. Mol. Biol. 64: 43-48. Levin, W., Welch, R. M., and Conney, A. H. (1968) Effect of phenobarbitol and other drugs on the metabolism and Uterotropic action of estradiol-17 beta and estrone. J. Pharmacol. Exp. Ther. 159: 362-371. Liehr, J. G., Ricci, M. J., Jefcoate, C. R., Hannigan, E. V., Hokanson, J. A., and Zhu, B. T. (1995) 4-Hydroxylation of estradiol by human uterine myometrium and myoma microsomes:Implications for the mechanism of uterine tumorigenesis. Proc. Natl. Acad. Sci. USA 92: 9220-9224. Linton, E. A., White, N., de Tineo, O. L., and Jeffcoate, S. L. (1981) 2-Hydroxyestradiol inhibits prolactin release from the superfased rat pituitary gland. J. Endocrinol. 90:315-322. Litwack, G., Ketterer, B., and Arias, I. M. (1971) Ligandin: a hepatic protein which binds steroids, bilirubin, carcinogens and a number of exogenous organic anions. Nature 234(5330):466-467. Lund, A. E., Shankland, D. L., Chinn, C., and Yim, G. K. W. (1978) Similar cardiovascular toxicity of the pesticide chlordimeform and lidocaine. Toxicol. Appl. Pharmacol. 44:357-365. Lyttle, C. R., and Desombre, E. R. (1977) Uterine peroxidase activity as a maker for estrogen action. Proc. Natl. Acad. Sci. U S A 74: 3162-3166. Mackenzie, P., and Hänninen, O. (1980) A sensitive kinetic assay for UDP Glucuronosyltransferase using 1-naphthol as substrate. Anal. Biochem. 109: 362-368. Mackenzie, P. I., Owens, I. S., Burthell, B., Bock, K. W., Bairoch, A., Belangen, A., Fournel-Gigleux, S., Green, M., Hum, D. W., Iyanagi, T., Lancet, D., Louisot, P., Magdalou, J., Chowdhury, J. R., Ritter, J. K., Schachter, H., Tephly, T. R., Tipton, K. F., and Nebert, D. W. (1997) The UDP glycosyltransferase gene superfamily: recommended nomenclature update based on evolutionary divergence. Pharmacogenetics 7:255-269. MacLusky, N. J., Naftolin, F., Krey, L. C., and Franks, S. (1981) The catechol estrogen. J. Steroid Biochem. 15:111-124. Marchand, P., Le Bizec, B., Gade, C., Mouteau, F., and Andr’e, F. (2000) Ultra trace detection of a wide rage of anabolic steroids in meat by gas chromatography coupled to mass spectrometry. J. Chromatogr. A 867:219-233. Martignoni, M., Monshouwer, M., Kanter, R., Pezzetta, D., Moscone, A., and Grossi, P. (2004) PhaseⅠand phaseⅡmetabolic activites are retained in liver slice from mouse, rat, dog, monkey and human after cryopreservation. Toxicol. In Vitro 18:121-128. Martucci, C., and Fishman, J. (1979) Impact of continuously administered cutechol on uterine growth and LH secretion. Endocrinology 105:1288-1292. Matsumoto, A. M., and Bremner, W. J. (1984) Modulation of pulsatile gonadotropin secretion by testosterone in men. J. Clin. Endocrinol. Metab. 58:609-614. Mesia-Vela, S., Sanchez, R. I. Li, J. J., Li, S. A., Conney, A. H., and Kauffman, F. C. (2002) Cateechol estrogen formation in liver microsomes from female ACI and Sprague-Dawley rats:comparison of 2-and 4-hydroxylation revisited. Carcinogenesis 23: 1369-1372. Mylchreest, E., Cattley, R. C., and Foster, M. D. (1998) Male reproductive tract malformations in rats following gestational and lactational exposure to Di(n-butyl) Phthalate:An antiandrogenic mechanism? Toxicol. Sci. 43:47-60. Nebert, D. W., and Mckinnon, R. A. (1994) Cytochrome P450: evolution and functional diversity. Prog. Liver Dis. 12:63-97. O’Connor, J. C., Frame, S. R., Davis, L. G., and Cook, J. C. (1999) Detection of the environmental antiandrogen p.p’-DDE in CD and Long-Evans rats using a tier I screening battery and a Hershberger assay. Toxicol. Sci. 51:44-53. Ogura, K., Kajita., J., Narihata, H., Watabe, T., Ozawa, S., Nagata, K., Yamazoe, Y. and Kato, R. (1989) Cloning and sequence analysis of a rat liver cDNA encoding hydroxysteroid sulfotransferase. Biochem. Biophys. Res. Commun. 165:168-174. Omura T., and Sato R. (1964) The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J. Biol. Chem. 239:2370-2378. Oropeza-Hern’andez, L. F., Sierra-Santoyo, A., Cebria’n, M. E., Manno, M. and Albores, A. (2001) Ovariectomy modulates the response of some cytochrome P450 isozymes to lindane in the rat. Toxicol. Lett. 124:91-99. Oropeza-Hernandez LF, Lopez-Romero R., and Albores A. (2003) Hepatic CYP1A, 2B, 2C, 2E and 3A regulation by methoxychlor in male and female rats. Toxicol. Lett. 144:93-103. Osano, O., Admiraal, W., Klamer, H. J. C., Pastor, D., and Bleeker, E. A. J. (2002) Comparative toxic and genotoxic effects of chloroacetanilides, formamidines and their degradation products on Vibrio fischeri and Chironomus riparius. Environ. Pollu. 119:195-202. Parvizi, N., and Ellendorff, F. (1983) Catechol estrogens in the brain: neuroendocrine integration. J. Steroid Biochem. 19:615-618. Pfister, W., Chin, C., Noland, V., and Yim, G. K. W. (1978) Similar pharmacological acitions of chlordimeform and local anesthetics. Pestic. Biochem. Physiol. 9:148-156. Pinnella, K.D., Cranmer, B.K., Tessari, J.D., Cosma, G. N., and Veeramachaneni, D.N. (2001) Gas chromatographic determination of catecholestrogens following isolation by solid by solid-phase extraction. J. Chromatogr. B 758:145-152. Poirier, D., Bydal, P., Tremblay, M.R., Sam, K. M., and Luu, T. V. (2001) Inhibitors of type II 17beta-hydroxysteroid dehydrogenase. Mol. Cell Endocrinol. 171:119-128. Qian, Y. M., Sun, X. J., Tong, M. H., Li, X. P., Richa, J., and Song, W. C. (2001) Targeted disruption of the mouse estrogen sulfotranaferase gene reveals a role of estrogen metabolism in intracrine and paracrine estrogen regulation. Endocrinology 142: 5342-5350. Ray, S., Xu, F., Li, P., Sanchez, N. S., Wang, H., and Das, S. K. (2007) Increased level of cellular Bip critically determines estrogenic potency for a xenoestrogen kepone in the mouse uterus. Endocrinology 148: 4774-4785. Robinson, C. P., and Smith, P. W. (1977) Lack of involvement of monoamine oxidase inhibition in the lethality of acute poisoning by chlordineform. J. Toxicol. Environ. Health 3:565-568. Savas, ű., Christou, M., and Jefcoate, C. R. (1993) Mouse endometriun stromal cells express a polycyclic aromatic hydrocarbon-inducible cytochrome p450 in mouse embryo fibroblasts (P450EF). Carcinogenesis 14: 2013-2018. Sawyer, C. H. (1975) Some recent developments in brain-pitaitary-Ovarian physiology Neuroendocrinology 17:97-125. Schneider, J., Huh, M. M., Bradlow, H. L., and Fishman, J. (1984) Antiestrogen action of 2-hyclroxyestrone on McF-7 human breast cancer cells. J. Biol. Chem. 259:4840-4845. Seegers, J. C., Aveling, M. L., Van Aswegen, C. H., Cross, M., Koch, F., and Joubert, W. S. (1989) The cytotoxic effects of estradiol-17β, catecholestradiols and methoxyestradiols on dividing MCF-7 and Hela cells. J. Steroid Biochem. Mol. Biol. 32: 797-809. Sheckter, C. B., Matsumoto, A. M., and Bremner, W. J. (1989) Testosterone admiuistration inhibits gonadotropin secretion by an effect on the human pituitary J. Clin. Endocrinol. Metab. 68:397-401. Shin, D. H., and Hsu W. H. (1994) Influence of the formamidine pesticide amitraz and its metabolites on porcine myometrial contractility:involvement of α2-adrenoceptors and Ca2+ channels. Toxicol. Appl. Pharmacol. 128:45-49. Smith, B. S. (1981) Male characteristics on female mud snails caused by antifouling bottom paints. J. Appl. Toxicol. 1(1):22-25. Song, C. S., Echchgadda, I., Baek, B. S., Ahn, S. C., Oh, T., Roy, A. K., and Chatterjee, B. (2001) Dehydroepiandrosterone sulfotransferase gene induction by bile acid activated farnesoid X receptor. J. Biol. Chem. 276:42549-42556. Sonnenschein, C., and Soto, A. M. (1998) An updated review of environmental estrogen and androgen mimics and antagonists. J. steroid Biochem. Mol. Biol. 65:143-150. Straube, E., Straube, W., Krűger, E., Bradatsch, M., Jacob-Meisel, M., and Rose, H. J. (1999) Disruption of male sex hormones with regard to pesticides: Pathophyaiological and regulatory aspects. Toxicol. Lett. 107:225-231. Suchar, L. A., Chang, R. L., Rosen, R. T., Lech, J., and Conney, A. H. (1995) High performance liquid chromatography separation of hydroxylated estradiol metabolites: formation of estradiol metabolites by liver microsomes from male and female rats. J. Pharmacol. Exp. Ther. 272:197-206. Suchar, L. A., chang, R. L., Thomas, P.E., Rosen, R.T., Lech, T., and Commey, A. H. (1996) Effect of phenobarbital, dexamethasone and 3-methylcholanthrene administration on the metabolisa of 17β-Estradiol by liver microsomes from female Long-Evans rats. Endocrinology 137: 663-676. Taccheo, M. B., De Paoli, M., and Spessoto, C. (1988) Determination of total amitraz residue in honey by electron capture capillary gas chromatography-A simplified method. Pestic. Sci. 23:59-64. Ueng, T. H., Hung, C. C., Wang, H. W., and Chan, P. K. (2004) Effects of amitraz on cytochrome P450-dependent monooxygenases and estrogenic activity in MCF-7 human breast cancer cells and immature female rats. Food Chem. Toxicol. 42:1785-1794. Vansell, N. R., and Klaassen, C. D. (2002) Increase in rat liver UDP-glucuronosyltransferase mRNA by microsomal enzyme inducers that enhance thyroid hormone glucuronidation. Drug Metab. Dispos. 30:240-246. Wang, C. M., Narahashi, T., and Fukami, J. I. (1975) Mechanism of meuromuscular block by chlordimeform. Pestic. Biochem. Physiol. 5:119-125. Watanabe, K., Takanashi, K., Imaoka, S., Funat, Y., Kawano, S., Inoue, K., Kamataki, T., Takagi, H., and Yoshizawa, I. (1991) Comparison of cytochrome P-450 Species which catalyze the hydroxylations of the aromatic ring of estradiol and estradiol 17-Sulfate. J. Steroid Biochem. Biol. 38:737-743. Waxman, D. J. (1984) Rat hepatic cytochrome P-450 isoesoenzyme 2C. Identification as a male-specific, developmentally induced steroid 16α-hydroxylase and comparison to a female-specific cytochrome P-450 isoenzyme. J. Biol. Chem. 259:15481-15490. Whitlock, J. P. (1999) Induction of cytochrome P4501A1. Annu. Rev. pharmacol. Toxicol. 39:103-125. Wilson, A. M., and Reed, G. A. (2001) Predominant 4-hydroxylation of estradiol by constitutive cytochrome P450s in the female ACI rat liver. Carcinogenesis 22: 257-263. Wilson, V. S., and LeBlanc, G. A. (1998). Endosulfan elevates testosterone biotransformation and clearance in CD-1 mice. Toxicol. Appl. Pharmacol. 148:158-168. Wilson, V. S., and Leblanc, G. A. (1999) The contribution of hepatic inactivation of testosterone to the lowering of serum testosterone levels by ketoconazole. Toxicol. Sci. 54:128-137. Wood, A.W., Dene, E. R., Paul, E. T., and Wayne, L. (1983) Regio and steroselection metabolism of two C19 steroids by five highly purified and recomstitues rat hepatic cytochrome P450 isozymes. J. Biol. Chem. 258:8839-8847. Yang, Y., Sharma, R., Zimniak, P., and Awasthi, Y. C. (2002) Role of alpha class glutathione S-transferases as antioxidant enzymes in rodent tissues. Toxicol. Appl. Pharmacol. 182(2):105-115. Zhu, B. T., and liehr, J. G. (1994) Quercetin increases the severity of estradiol-indaced tumorigenesis in hamster kidney. Toxicol. Appl. Pharmacol. 125:149-158. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37348 | - |
dc.description.abstract | 三亞蟎為一防治果樹蟎類及牛、羊蜱類等用途之甲咪類(formamidine)農業用藥。本研究主要目的,在探討三亞蟎調控大鼠睪固酮及雌素二醇的代謝作用,及血清中睪固酮(testosterone)及雌素二醇(17β-estradiol)含量所扮演的角色。內分泌干擾物的定義為,外來的化學物質具有干擾內生性荷爾蒙在生合成,分泌、傳輸、結合及生理功用,體內的代謝、排泄等方面的機制者稱之。因此本研究假設三亞蟎為一內分泌干擾物質,具調控睪固酮及雌素二醇在大鼠的代謝及血清中的含量。首先本研究進行睪固酮、雌素二醇及代謝產物在大鼠血清中,及微粒體分析方法的建立。分別以液相層析附串聯式質譜儀(liquid chromatography- tandem mass spectrometry, LC/MS),對睪固酮代謝產物及睪固酮的鑑定與分析,以及以氣相層析附質譜(gas chromatography-mass spectrometry, GC/MS)及電子捕獲式檢出器(gas chromatography-electron capture detector, GC-ECD),對雌素二醇代謝產物及雌素二醇在血清中的鑑定與分析。接著為瞭解三亞蟎對大鼠肝臟P450代謝酵素活性的影響,雄性及雌性大鼠以腹腔注射的方式,分別處理25及50 mg/kg三亞蟎藥劑持續五及七天。切除卵巢雌性大鼠,除處理相同劑量三亞蟎外,另以腹腔注射處理0.5 mg/kg雌素二醇。大鼠在經處理後,分別製備肝臟微粒體(microsome),以進行實驗。在P450含量及erythromycin N-demethylase活性部分,雄性大鼠在以50 mg/kg處理後,活性分別增加39及68 %。而雌性大鼠則在處理50 mg/kg後,分別增加51及81%。切除卵巢雌性大鼠,在共同處理0.5 mg/kg雌素二醇及50 mg/kg三亞蟎後,活性分別增加178及71%。本研究再以相同劑量處理雄、雌性大鼠,觀察對phaseⅡ酵素活性及蛋白表現的影響。三亞蟎對葡萄糖醛酸基轉移酶(UDP-Glucuronosyltransferase)在雄及雌性大鼠均呈劑量關係,同時雄性大鼠分別增加39%及0.8倍,雌性大鼠則分別增加57及113%。麩胱甘肽轉移酶(glutathione-S-transferase)在雄性大鼠的活性,隨處理劑量的增加而增加,在以50 mg/kg處理時活性增加一倍,在雌性大鼠於25 mg/kg處理時降低0.8倍,但在50 mg/kg處理時則增加40%。對氮-乙醯基轉移酶(N-acetyltransferase)雄性大鼠活性在50 mg/kg處理後,顯著增加2.0倍,雌性大鼠則分別增加72及86%。對兒茶酚-O-甲基轉移酶( catechol O-methyltransferase)在雄及雌性大鼠均不會產生影響。對硫基轉移酶(sulfo-transferase)在雄性大鼠呈顯著增加的趨勢,在以25 mg/kg處理時,活性增加46%,以50 mg/kg處理後,活性則增加1.13倍。在雌性大鼠則有降低活性的趨勢,以25 mg/kg處理時,活性下降至0.73倍,而50 mg/kg處理後,活性降低0.3倍呈顯著性的降低。為證實三亞蟎對SULT活性影響的性別差異,本研究進行三亞蟎對SULT1E2及SULT2A1此兩種SULT isoform蛋白表現的測試。在以西方墨點分析SULT1E2的蛋白結果,以雄性大鼠的表現較雌性大鼠為顯著,但三亞蟎對此蛋白的影響,雄性大鼠則隨處理劑量的增加,而降低蛋白表現的趨勢,雌性大鼠則是隨處理劑量的增加,而增加蛋白的表現。至於在對SULT2A1的蛋白表現,以雌性大鼠的表現較雄性大鼠為顯著。但三亞蟎對此蛋白的影響,雄性大鼠隨處理劑量的增加,而增加蛋白表現,雌性大鼠則是隨處理劑量的增加,而呈現降低蛋白表現的趨勢。在睪固酮代謝部分,液相層析分析結果顯示,以50 mg/kg三亞蟎處理後,雄性大鼠肝臟微粒體代謝產生睪固酮6β-, 16α-以及2β-羥基代謝產物的生成,分別增加2.0,1.4及2.8倍。而在雌性大鼠則分別增加1.5,2.9以及3.0倍。同時三亞蟎亦增加雌性大鼠8.6倍在16β-羥基睪固酮,以及另一代謝產物androstenedione的代謝生成。16β-羥基睪固酮以及androstenedione的代謝生成,在雄性大鼠則顯示分別增加1.7及2.6倍。三亞蟎在對切除卵巢及外加雌素二醇後,則只對睪固酮6β-羥基代謝產物的生成,顯示1.5倍的增加,但對其他的羥基代謝產物則無影響。在雌素二醇代謝方面,以氣相層析分別結果顯示,三亞蟎對肝臟微粒體代謝雌素二醇,在雄性大鼠分別增加1.7及3.6倍2-羥基雌素二醇及estrone的產生,而對雌性大鼠則增加1.9及3.1倍,但三亞蟎對切除卵巢雌性大鼠的肝臟微粒體,代謝雌素二醇的能力則無影響。除了以肝臟微粒體,探討三亞蟎對睪固酮及雌素二醇代謝的能力外,本研究另進行以三亞蟎處理後,大鼠血清中睪固酮、雌素二醇以及代謝產物濃度的測定。雄性大鼠在經三亞蟎處理後,血清中睪固酮及代謝產物2β-羥基睪固酮的濃度,分別增加12及20倍。而切除卵巢雌性大鼠在外加雌素二醇且經三亞蟎處理後,顯示會降低6.7倍血清中雌素二醇的濃度,但代謝產物2-羥基雌素二醇在血清中的濃度則反而增加。由上述各實驗結果顯示,三亞蟎能誘導大鼠肝臟對睪固酮及雌素二醇代謝的能力,且能因此而影響血清中睪固酮及雌素二醇的濃度,研究結果呈現,三亞蟎藥劑具內分泌干擾作用。 | zh_TW |
dc.description.abstract | The present study has investigated the ability of amitraz (N’-(2,4-dimethylphenyl)-N-[[2,4-dimethylphenyl]imino]methyl)-N-methanimidamide), a formamidine insecticide widely used to control eriophyid mites on pears and mange in animals, to modulate testosterone and 17β-estradiol (E2) metabolism and to alter the circulating levels of the hormones in rats. Endocrine-disrupting chemicals (EDCs) are exogenous agents that interfere with the production, release, transport, metabolism, binding, action, or elimination of the natural hormones in the body responsible for the maintenance of homeostasis and the regulation of developmental processes. The main hypothesis of this study was that amitraz is an EDC which has the ability to modulate testosterone and E2 metabolism and to alter the circulating levels of the hormones in rats. To test the hypothesis, the present study established analytical methods to detect and identify testosterone metabolites in rat serum and microsomes using high performance liquid chromatography-ultraviolet detector and tandem mass spectrometry and to detect E2 and metabolites using gas chromatography equipped with electron capture detector and mass spectrometry. To determine the effects of amitraz on liver cytochrome P450 content and erythromycin N-demethylase activity, amitraz was administered intraperitoneally at 25 and 50 mg/kg once daily for 5 and 7 days to male and female rats or to ovariectomized (OVX) female rats treated with 0.5 mg/kg E2. The results showed that in male rats, 50 mg/kg amitraz increased respective 39% and 68% of P450 and erythromycin N-demethylase activities. In female rats, 50 mg/kg of amitraz resulted in 51% and 81% increases of P450 content and erythromycin N-demethylase activity. In OVX female rats, cotreatment with E2 and 50 mg/kg of amitraz produced 178% and 71% increases of the aforementioned monooxygenase content or activity. The effects of amitraz on liver phase Ⅱ enzymes including uridine diphosphate-glucuronosyltransferase (UGT),glutathione S-transferase (GST), N-acetyltransferase (NAT), catechol O-methyltransferase (COMT), and sulfotransferase (SULT) activities were also studied. The results showed that in male rats, 25 mg/kg amitraz resulted in respective 39 and 46% increases of UGT and SULT activities. Amitraz at 50 mg/kg produced 0.8-, 1.0-, 2.0-, and 1.13-fold increases of UGT, GST, NAT and SULT enzymes activities, respectively. In female rats, 25 mg/kg amitraz produced 0.8- and 0.73-fold decreases of GST and SULT activities and 72% and 57% increases of NAT and UGT activities, respectively. Amitraz at 50 mg/kg produced 113%, 40%, and 86% increases of UGT, GST, and NAT activities, but decreased SULT by a 0.3-fold, respectively. The results of immunoblot analysis indicated that SULT 1E2 and 2A1 protein showed sex differences in their responses to amitraz treatment. Amitraz showed no effects on COMT activities of male and female rats. The results of testosterone metabolism studies of the liver of male and female rats showed that amitraz at the dose of 50 mg/kg produced respective 2.0-, 1.4-, and 2.8-fold increases of the ability of liver microsomes to metabolize testosterone to 6β-, 16α-, and 2β- hydroxylated products in male rats and 1.5-, 2.9-, and 3.0-fold increases in female rats. The insecticide resulted in an 8.6-fold increase of 16β-OH-testosterone formation in female rats and 2.6- and 1.7-fold increases of androstenedione formation in males and females, respectively. Amitraz increased testosterone 6β-hydroxylation by a 1.5-fold and had no effects on other metabolites formation in OVX and E2-treated female rats. The results of E2 metabolism on the liver of male and female rats showed that amitraz produced respective 1.7- and 3.6-fold increases of the capacity of liver microsomes to metabolize E2 to 2-OH-E2 and estrone in male rats and 1.9- and 3.1-fold increases in females. The formamidine did not have effects on E2 metabolism in OVX and E2-treated female rats. In male rat serum, amitraz increased testosterone and 2β-OH-testosterone concentrations by 12- and 20-fold, respectively. In OVX and E2-treated female rat serum, the insecticide produced a 6.7-fold decrease of E2 concentration and an increase of 2-OH-E2 concentration. The present findings show that amitraz induces testosterone and E2 metabolism in the liver and decreases the hormone concentrations in the serum of rats. These findings also demonstrate that amitraz is an endocrine disruptor. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T15:25:09Z (GMT). No. of bitstreams: 1 ntu-97-D90447004-1.pdf: 932535 bytes, checksum: ad09a1350bf498a2102bf610424cdc7f (MD5) Previous issue date: 2008 | en |
dc.description.tableofcontents | 目錄------------------------------------------------------------------------------------ Ⅰ
表目錄--------------------------------------------------------------------------------- Ⅳ 圖目錄--------------------------------------------------------------------------------- Ⅴ 中文摘要------------------------------------------------------------------------------ 1 英文摘要------------------------------------------------------------------------------ 4 研究背景 農藥與內分泌干擾------------------------------------------------------------------ 7 固醇類荷爾蒙 (steroid hormone) 的代謝-------------------------------------- 9 細胞色素P450單氧酶(Cytochromes P450)在代謝上所扮演的角色-- 10 Phase II酵素對固醇類荷爾蒙的代謝作用------------------------------------- 12 三亞蟎之基本資料------------------------------------------------------------------ 13 雌素二醇與睪固酮目前的分析技術--------------------------------------------- 17 研究目的------------------------------------------------------------------------------ 19 研究方法與步驟 動物試驗 未經手術實驗大鼠------------------------------------------------------------------ 22 卵巢切除實驗大鼠------------------------------------------------------------------ 22 藥品與試劑--------------------------------------------------------------------------- 23 動物試驗處理方式 腹腔注射投予三亞螨觀察對雄大鼠生殖器官影響之研究------------------ 23 腹腔注射投予三亞螨觀察對雌大鼠子宮過氧化酵素活性之研究--------- 23 腹腔注射投予三亞螨觀察對雄、雌大鼠及卵巢切除雌大鼠肝臟酵素活性之研究------------------------------------------------------------------------------ 24 肝臟微粒體及細胞質之製備------------------------------------------------------ 24 酵素活性測定 子宮過氧化酵素製備及活性之測定--------------------------------------------- 25 Cytochrome P450含量測定-------------------------------------------------------- 25 Erythromycin N-demethylase活性測試------------------------------------------ 26 PhaseΠ酵素活性測試 尿苷二磷酸葡萄醛轉移酶(UDP-glucuronosyl transferase, UGT)活性測試--------------------------------------------------------------------------------------- 26 麩胱甘肽轉移酶(glutathione S-transferase, GST)活性測試-------------- 27 N-乙醯基轉移酶(N-acetyltransferase, NAT)活性測試--------------------- 27 硫基轉移酶(Sulfotransferase, SULT)活性測試----------------------------- 27 兒茶酚-O-甲基轉移酶(catechol O-methyltransferase, COMT)活性測試------------------------------------------------------------------------------------------ 28 以西方墨點法(Western Blot)分析硫基轉移酵素蛋白表現------------------ 28 睪固酮代謝產物生成實驗--------------------------------------------------------- 29 雌素二醇代謝產物生成實驗------------------------------------------------------ 29 睪固酮、雌素二醇、三亞螨及其代謝產物之分析 睪固酮及代謝產物的分析--------------------------------------------------------- 29 睪固酮及代謝產物在血清中之分析--------------------------------------------- 30 睪固酮及代謝產物的儀器分析--------------------------------------------------- 30 血清中睪固酮代謝產物LC/MS/MS的鑑定------------------------------ 30 雌素二醇及代謝產物之分析------------------------------------------------------ 31 雌素二醇及代謝產物衍生化反應------------------------------------------------ 31 血清中雌素二醇及代謝產物分析方法建立------------------------------------ 32 雌素二醇及代謝產物儀器分析條件--------------------------------------------- 32 雌素二醇及代謝產物氣相層析質譜儀的鑑定--------------------------------- 33 三亞螨及代謝產物之分析--------------------------------------------------------- 34 三亞螨工廠作業人員尿液中三亞螨及其代謝產物的分析------------------ 34 三亞蟎及代謝產物之分析儀器及條件------------------------------------------ 34 統計分析------------------------------------------------------------------------------ 35 結果 睪固酮、雌素二醇及其代謝產物在大鼠血清中之分析與鑑定---- 36 三亞螨及其代謝產物在人體尿液中之分析與鑑定--------------------------- 38 三亞螨對雄性大鼠生殖器官重量的影響--------------------------------------- 40 三亞螨對雌性大鼠子宮過氧化酵素之影響------------------------------------ 41 三亞螨對雄、雌性大鼠及卵巢切除雌性大鼠肝臟微粒體P450及erythromycin N-demethylation活性之影響------------------------------------- 41 三亞螨對雄、雌性大鼠肝臟微粒體及胞質中phase II 代謝酵素之影響 ------------------------------------------------------------------------------------------ 42 三亞螨對雄、雌性大鼠肝臟SULT蛋白表現的影響------------------------- 44 三亞蟎對雄、雌性大鼠及卵巢切除雌性大鼠肝臟微粒體testosterone hydroxylase活性的影響------------------------------------------------------------ 45 三亞螨對雄、雌性大鼠及卵巢切除雌性大鼠肝臟微粒體雌素二醇代謝活性之影響--------------------------------------------------------------------------- 46 三亞螨對雄性大鼠血清中睪固酮及代謝產物含量之影響------------------ 47 三亞螨對切除卵巢雌性大鼠血清中雌素二醇及代謝產物含量之影響------------------------------------------------------------------------------------------ 49 討論 睪固酮、雌素二醇及其代謝産物在血清中的分析鑑定---------------------- 50 三亞蟎及其代謝産物在人體尿液中的監測分析--------------------- 53 三亞蟎對雄性大鼠生殖器官重量及雌性大鼠子宫過氧化化酵素的影響------------------------------------------------------------------------------------------ 55 三亞蟎對雄、雌性大鼠及卵巢切除大鼠肝臟微粒體P450 content及erythromycin N-demethylation 活性的影響------------------------------------- 56 三亞蟎對雄、雌性大鼠肝臟微粒體及胞質phase Ⅱ代謝酵素之影響----- 58 三亞蟎對雄、雌性大鼠及卵巢切除雌性大鼠肝臟微粒體testosterone hythroxylase以及雌素二醇代謝活性的影響------------------------------------ 60 三亞蟎對雄性大鼠血清中睪固酮及代謝産物含量之影響------------------ 63 三亞蟎對切除卵巢雌性大鼠血清中雌素二醇及代謝産物含量之影響------------------------------------------------------------------------------------------ 64 參考文獻------------------------------------------------------------------------------ 67 表--------------------------------------------------------------------------------------- 82 圖--------------------------------------------------------------------------------------- 97 表目錄 Table 1. Linear regression equations of E2 and metabolites of human and rats samples in GC-ECD---------------------------------------- 82 Table 2. Average recoveries and detection limits of amitraz, BTS-27271, BTS-27919 and 2,4-dimethylaniline of human urine samples in GC-MS--------------------------------------------- 83 Table 3. Effect of treatment with amitraz on organ weights in male rats- 84 Table 4. Effects of treatment with amitraz on uterine peroxidase activity in female rats----------------------------------------------------------- 85 Table 5. Effects of treatment with amitraz on cytochrome P450 content and erythromycin N-demethylase activity in liver microsomes of male rats------------------------------------------------------------- 86 Table 6. Effects of treatment with amitraz on cytochrome P450 content and erythromycin N-demethylase activity in liver microsomes of OVX and E2-supplemented female rats------------------------- 87 Table 7. Effects of treatment with amitraz on cytochrome P450 content and erythromycin N-demethylase activity in liver microsomes of intact female rats--------------------------------------------------- 88 Table 8. Effects of treatment with amitraz on UGT, GST, NAT, COMT and SULT activities in the livers of male rats-------------------- 89 Table 9. Effects of treatment with amitraz on UGT, GST, NAT, COMT and SULT activities in the livers of female rats------------------ 90 Table 10. Effects of treatment with amitraz on testosterone metabolism by liver microsomes of male rats------------------------------------ 91 Table 11. Effects of treatment with amitraz on testosterone metabolism by liver microsomes of OVX female rats--------------------------- 92 Table 12. Effects of treatment with amitraz on testosterone metabolism by liver microsomes of female rats---------------------------------- 93 Table 13. Effects of treatment with amitraz on E2 metabolism by liver microsomes of male rats---------------------------------------------- 94 Table 14. Effects of treatment with amitraz on E2 metabolism by liver microsomes of OVX female rats------------------------------------- 95 Table 15. Effects of treatment with amitraz on E2 metabolism by liver microsomes of female rats-------------------------------------------- 96 圖目錄 Fig. 1. A representative HPLC chromatogram of testosterone and metabolites---------------------------------------------------------------- 97 Fig. 2. Scheme of HFBA derivatization reactions of E2 and metabolites before GC-ECD determination----------------------------------------- 98 Fig. 3. GC-ECD analyses of serum E2, 2-OH E2, and 4-OH E2 in rats------------------------------------------------------------------------- 99 Fig. 4. GC-MSD determination of E2, 2-OH E2, and 4-OH E2 after HFBA derivatization----------------------------------------------------- 100 Fig. 5. A representative GC-NPD chromatogram of amitraz and metabolites---------------------------------------------------------------- 101 Fig. 6. GC-MS chromatograms of amiraz and metabolites----------------- 102 Fig. 7. Effects of treatment with amitraz on sulfotransferase 1E2 protein in male and female rats-------------------------------------------------- 103 Fig. 8. Effects of treatment with amitraz on sulfotransferase 2A1 protein in male and female rats-------------------------------------------------- 104 Fig. 9. Densitometric analysis of amitraz on sulfotransferase 1E2 protein in male and female rats----------------------------------------- 105 Fig. 10. Densitometric analysis of amitraz on sulfotransferase 2A1 protein in male and female rats----------------------------------------- 106 Fig. 11. Effects of treatment with amitraz on serum testosterone and 2-OH-testosterone (2-OH-T) concentrations in male rats---------- 108 Fig. 12. LC-MS/MS analysis of serum 2 | |
dc.language.iso | zh-TW | |
dc.title | 三亞螨藥劑對大鼠體內睪固酮及雌素二醇代謝之調控作用 | zh_TW |
dc.title | Modulation of testosterone and 17β-estradiol metabolism by amitraz in rats | en |
dc.type | Thesis | |
dc.date.schoolyear | 96-2 | |
dc.description.degree | 博士 | |
dc.contributor.oralexamcommittee | 劉宗榮,李德章,鍾邦柱,黃金鼎 | |
dc.subject.keyword | 三亞螨,睪固酮,雌素二醇,代謝,內分泌干擾, | zh_TW |
dc.subject.keyword | amitraz,testosterone,estrogen,metabolism,endocrine disruption, | en |
dc.relation.page | 113 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2008-07-21 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 毒理學研究所 | zh_TW |
Appears in Collections: | 毒理學研究所 |
Files in This Item:
File | Size | Format | |
---|---|---|---|
ntu-97-1.pdf Restricted Access | 910.68 kB | Adobe PDF |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.