Please use this identifier to cite or link to this item:
標題: 運用蛋白質胼合物為生物指標評估多環芳香族碳 氫化合物及戴奧辛之環境暴露對雌性激素之活性 醌類代謝物累積組織劑量之影響
Application of protein adducts as biomarkers to assess the effects of environmental exposure to polycyclic aromatic hydrocarbons (PAHs) and dioxin on the cumulative tissue does of quinonoid metabolites of endogenous estrogen
作者: 楊宗洲
Yang, Tsung-Chou
關鍵字: biomarker
protein adduct
polycyclic aromatic hydrocarbon
出版社: 環境工程學系所
引用: 魏子翰 (2009) 同步分析人類血清白蛋白中萘及雌性激素醌類代謝物之蛋白質胼合 物。國立中興大學環境工程研究所碩士論文,台灣台中。 Ainslie DA, Morris MJ, Wittert G, Turnbull H, Proietto J, Thorburn AW. (2001) Estrogen deficiency causes central leptin insensitivity and increased hypothalamic neuropeptide Y. Int J Obes Relat Metab Disord. 25(11):1680-8. Badawi, A. F., Cavalieri, E. L., and Rogan, E. G. (2001) Role of human cytochrome P450 1A1, 1A2, 1B1, and 3A4 in the 2-, 4-, and 16alpha-hydroxylation of 17beta-estradiol. Metabolism. 50,1001-1003. Bernstein L, Yuan JM, Ross RK, Pike MC, Hanisch R, Lobo R, Stanczyk F, Gao YT, Henderson BE. (1990) Serum hormone levels in pre-menopausal Chinese women in Shanghai and white women in Los Angeles: results from two breast cancer case-control studies. Cancer Causes Control. 1(1):51-8. Bjorseth A, Ramdahl T. (1985) Sources and emissions of PAH. In: Emission Sources and Recent Progress in Analytical Chemistry Handbook of Polycyclic Aromatic Hydrocarbons, vol. 2. Marcel Dekker. Boverhof DR, Kwekel JC, Humes DG, Burgoon LD, Zacharewski TR. (2006) Dioxin induces an estrogen-like, estrogen receptor-dependent gene expression response in the murine uterus. Mol Pharmacol. 69(5):1599-606. Bray F, McCarron P, Parkin DM. (2004) The changing global patterns of female breast cancer incidence and mortality. Breast Cancer Res. 6(6):229-39. Brown LM, Gent L, Davis K, Clegg DJ. (2010) Metabolic impact of sex hormones on obesity. Brain Res. Brown NM, Manzolillo PA, Zhang JX, Wang J, Lamartiniere CA. (1998) Prenatal TCDD and predisposition to mammary cancer in the rat. Carcinogenesis. 19(9):1623-9. Burdick, A. D., Davis, J. W., 2nd, Liu, K. J., Hudson, L. G., Shi, H.,Monske, M. L., and Burchiel, S. W. (2003) Benzo(a)pyrene quinonesincrease cell proliferation, generate reactive oxygen species, and transactivate the epidermal growth factor receptor in breast epithelial cells.Cancer Res. 63, 7825–7833. Butterworth, M., Lau, S.S., Monks, T.J. (1996) 17β-Estradiol Metabolism by Hamster 102 Hepatic Microsomes: Comparison of Catechol Estrogen O-Methylation with Catechol Estrogen Oxidation and Glutathioe Conjugation. CRT. 9(4), 793-799. Cavalieri E, Rogan E, Chakravarti D. (2004) The role of endogenous catechol quinones in the initiation of cancer and neurodegenerative diseases. Methods Enzymol 382:293-319. Review. Cavalieri EL, Devanesan P, Bosland MC, Badawi AF, Rogan EG. (2002) Catechol estrogen metabolites and conjugates in different regions of the prostate of Noble rats treated with 4-hydroxyestradiol: implications for estrogen-induced initiation of prostate cancer. Carcinogenesis. (2):329-33. Cavalieri EL, Li KM, Balu N, Saeed M, Devanesan P, Higginbotham S, Zhao J, Gross ML, Rogan EG. (2002) Catechol ortho-quinones: the electrophilic compounds that form depurinating DNA adducts and could initiate cancer and other diseases. Carcinogenesis. (6):1071-7. Cavalieri EL, Stack DE, Devanesan PD, Todorovic R, Dwivedy I, Higginbotham S, Johansson SL, Patil KD, Gross ML, Gooden JK, Ramanathan R, Cerny RL, Rogan EG. (1997) Molecular origin of cancer: catechol estrogen-3,4-quinones as endogenous tumor initiators. Proc Natl Acad Sci U S A. 94(20):10937-42. Cavalieri EL. (1994) Minisymposium on endogenous carcinogens: the catechol estrogen pathway. Polycyclic Aromaric Compounds, 6. 223-228. Cavalieri, E., Chakravarti, D., Guttenplan, J. (2006) Catechol Estrogen Quinones as Initiators of Breast and Other Human Cancers: Implications for Biomarkers of Susceptibility and Cancer Prevention. Biochim. Biophys. Acta. 1766,63-78. Chakravarti D, Mailander PC, Li KM, Higginbotham S, Zhang HL, Gross ML, Meza JL, Cavalieri EL, Rogan EG. (2001) Evidence that a burst of DNA depurination in SENCAR mouse skin induces error-prone repair and forms mutations in the H-ras gene. Oncogene. 20(55):7945-53. Chan MY, Huang H, Leung LK. (2010) 2,3,7,8-Tetrachlorodibenzo-para-dioxin increases aromatase (CYP19) mRNA stability in MCF-7 cells. Mol Cell Endocrinol. 317(1-2):8-13. Charles A. Menzie, Bonnie B. Potocki, and Joseph Santodonato. (1992) Exposure to carcinogenic PAHs in the environment. Environ. Sci. Technol. 26 (7),1278-1284. Cherng SH, Lin ST, Lee H. (1996) Modulatory effects of polycyclic aromatic 103 hydrocarbons on the mutagenicity of 1-nitropyrene: a structure-activity relationship study. Mut Res 367(4):177–85. Chetrite GS, Cortes-Prieto J, Philippe JC, Wright F, Pasqualini JR. (2000) Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues. J Steroid Biochem Mol Biol. 72(1-2):23-7. Clegg DJ, Benoit SC, Barrera JG, Woods SG, Seely RJ, (2003b) Fisher ME. Sex hormones determine body fat distribution and sensitivity to adiposity signals. Appetite 40,324. Clegg DJ, Benoit SC, Barrera JG, Woods SG. (2003a) Estrogen mediates body fat distribution and brain sensitivity to adiposity signals. Diabetes 52. Clegg DJ, Benoit SC, Riedy CA, Woods SG, Smith KA. (2003c) Differential sensitivity to central leptin and insulin in male and female rats. Diabetes. 52:682-687. Clegg DJ, Brown LM, Woods SC, Benoit SC. (2006) Gonadal hormones determine sensitivity to central leptin and insulin. Diabetes. 55(4):978-87. Clemons M, Goss P. (2001) Estrogen and the risk of breast cancer. N Engl J Med. 344(4):276-85. Review. Dawling S, Hachey DL, Roodi N, Parl FF. (2004) In vitro model of mammary estrogen metabolism: structural and kinetic differences between catechol estrogens 2- and 4-hydroxyestradiol. Chem Res Toxicol. 17(9):1258-64. Fernandez, S.V., Russo, I.H., Russo, J. (2006) Estradiol and its Metabolites 4-Hydroxyestradiol and 2-Hydroxyestradiol Induce Mutations in Human Breast Epithelial Cells. Int. J. Cancer. 118,1862-1868. Fujii-Kuriyama Y, Mimura N. (2005) Molecular mechanisms of AhR functions in the regulation of cytochrome P450 genes. Biochem Biophys Res Commun. 228:311-7. Gammon MD, Sagiv SK, Eng SM, Shantakumar S, Gaudet MM, Teitelbaum SL, Britton JA, Terry MB, Wang LW, Wang Q, Stellman SD, Beyea J, Hatch M, Kabat GC, Wolff MS, Levin B, Neugut AI, Santella RM. (2004) Polycyclic aromatic hydrocarbon-DNA adducts and breast cancer: a pooled analysis. Arch Environ Health. 59(12):640-9. Gammon MD, Wolff MS, Neugut AI, Eng SM, Teitelbaum SL, Britton JA, Terry MB, Levin B, Stellman SD, Kabat GC, Hatch M, Senie R, Berkowitz G, Bradlow HL, Garbowski G, Maffeo C, Montalvan P, Kemeny M, Citron M, Schnabel F, Schuss A, Hajdu S, Vinceguerra V, Niguidula N, Ireland K, Santella RM. (2002) Environmental 104 toxins and breast cancer on Long Island. II. Organochlorine compound levels in blood. Cancer Epidemiol Biomarkers Prev. 11(8):686-97. Granath.F., Ehrenberg.L. and Tomqvist.M. (1992) Degree of alkylation of macromolecules in vivo from variable exposure. Mutat. Res. 284, 297-306. Guengerich FP. (1989) Characterization of human microsomal cytochrome P-450 enzymes. Annu Rev Pharmacol Toxicol. 29:241-64. Review. Hayes, C. L., Spink, D. C., Spink, B. C., Cao, J. Q., Walker, N. J., and Sutter, T. R. (1996) 17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1B1. Proc. Natl. Acad. Sci. U. S. A. 93,9776-9781. Heine PA, Taylor JA, Iwamoto GA, Lubahn DB, Cooke PS. (2000) Increased adipose tissue in male and female estrogen receptor-alpha knockout mice. Proc Natl Acad Sci U S A. 97(23):12729-34. Hu Y, Li G, Xue X, Zhou Z, Li X, Fu J, Cohen B, Roy N, Li D, Sun J, Nan P, Tang MS, Qu Q. (2007) PAH-DNA adducts in a Chinese population: relationship to PAH exposure, smoking and polymorphisms of metabolic and DNA repair genes. Biomarkers 13(1):27-40. Huang CS, Lin CH, Lu YS, Shen CY (2010) Unique features of breast cancer in Asian women--breast cancer in Taiwan as an example. J Steroid Biochem Mol Biol. 118(4-5):300-3. Huang Z, Fasco MJ, Figge HL, Keyomarsi K, Kaminsky LS. (1996) Expression of cytochromes P450 in human breast tissue and tumors. Drug Metab Dispos. 24(8):899-905. IARC International Agency for Research on Cancer. (1973) Certain polycyclic aromatic hydrocarbons and heterocyclic compounds. Monograph on the evaluation of carcinogenic risks of the chemical to man. Vol. 3. Lyon, France: World Health Organization. IARC International Agency for Research on Cancer. (1997) Polycholorinated Dibenzo-para-dioxins and Polycholorinated Dibenzofurans. Monograph on the evaluation of carcinogenic risks of the chemical to man. Vol. 69. Lyon, France. IARC International Agency for Research on Cancer. (2002) Some traditional herbal medicines, some mycotoxins, naphthalene and styrene. Monograph on the evaluation of carcinogenic risks of the chemical to man. Vol. 82. Lyon, France. 105 Jefcoate CR, Liehr JG, Santen RJ, Sutter TR, Yager JD, Yue W, Santner SJ, Tekmal R, Demers L, Pauley R, Naftolin F, Mor G, Berstein L. (2000) Tissue-specific synthesis and oxidative metabolism of estrogens. J Natl Cancer Inst Monogr. (27):95-112. Review. Kleiner HE, Vulimiri SV, Reed MJ, Uberecken A, DiGiovanni J. (2002) Role of cytochrome P450 1a1 and 1b1 in the metabolic activation of 7,12-dimethylbenz[a]anthracene and the effects of naturally occurring furanocoumarins on skin tumor initiation. Chem Res Toxicol. 15(2):226-35. Lareef MH, Garber J, Russo PA, Russo IH, Heulings R, Russo J. (2005) The estrogen antagonist ICI-182-780 does not inhibit the transformation phenotypes induced by 17-beta-estradiol and 4-OH estradiol in human breast epithelial cells. Int J Oncol. 423-9. Lemon HM, Heidel JW, Rodriguez-Sierra JF.(1992) Increased catechol estrogen metabolism as a risk factor for nonfamilial breast cancer. Cancer. 69(2):457-65. Li D, Wang M, Dhingra K, Hittelman WN. (1996) Aromatic DNA adducts in adjacent tissues of breast cancer patients: clues to breast cancer etiology. Cancer Res. 56(2):287-93. Li JJ, Gonzalez A, Banerjee S, Banerjee SK, Li SA. (1993) Estrogen carcinogenesis in the hamster kidney: role of cytotoxicity and cell proliferation. Environ Health Perspect. 5:259-64. Li JJ, Li SA. (1987) Estrogen carcinogenesis in Syrian hamster tissues: role of metabolism. Fed Proc. 46(5):1858-63. Li KM, Todorovic R, Devanesan P, Higginbotham S, Kofeler H, Ramanathan R, Gross ML, Rogan EG, Cavalieri EL. (2004) Metabolism and DNA binding studies of 4-hydroxyestradiol and estradiol-3,4-quinone in vitro and in female ACI rat mammary gland in vivo. Carcinogenesis. 25(2):289-97 Liehr JG, Ricci MJ. (1996) 4-Hydroxylation of estrogens as marker of human mammary tumors. Proc Natl Acad Sci U S A. 93(8):3294-6. Liehr JG, Ricci MJ. (1996) 4-Hydroxylation of estrogens as marker of human mammary tumors. Proc Natl Acad Sci U S A. 93(8):3294-6. Lin PH, Lin CH, Huang CC, Chuang MC, Lin P. (2007) 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces oxidative stress, DNA strand 106 breaks, and poly(ADP-ribose) polymerase-1 activation in human breast carcinoma cell lines. Toxicol Lett. 172(3):146-58. Lin YC, Lee WJ, Chen SJ, Chang-Chien GP, Tsai PJ. (2008) Characterization of PAHs exposure in workplace atmospheres of a sinter plant and health-risk assessment for sintering workers. J Hazard Mater. 158(2-3):636-43. Lin, P.H., Chen, D.R., Wang, T.W., Lin, C.H., Chuang, M.C. (2009) Investigation of the cumulative tissue doses of naphthoquinones in human serum using protein adducts as biomarker of exposure. Chem.Biol.Interact. 181(1),107-114. Lin, T.C., Chang, F.H., Hsieh, J.H. (2002) Characteristics of Polycyclic Aromatic Hydrocarbons and Total Suspended Particulate in Indoor and Outdoor Atmosphere of a Taiwanese Temple. J. Hazard. Mater. 95, 1-12. Lo YL, Yu JC, Huang CS, Tseng SL, Chang TM, Chang KJ, Wu CW, Shen CY. (1998) Allelic loss of the BRCA1 and BRCA2 genes and other regions on 17q and 13q in breast cancer among women from Taiwan (area of low incidence but early onset). Int J Cancer. 79(6):580-7. Lu F, Zahid M, Saeed M, Cavalieri EL, Rogan EG. (2007) Estrogen metabolism and formation of estrogen-DNA adducts in estradiol-treated MCF-10F cells. The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin induction and catechol-O-methyltransferase inhibition. J Steroid Biochem Mol Biol. 105(1-5):150-8. Lu F, Zahid M, Saeed M, Cavalieri EL, Rogan EG. (2007) Estrogen metabolism and formation of estrogen-DNA adducts in estradiol-treated MCF-10F cells. The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin induction and catechol-O-methyltransferase inhibition. J Steroid Biochem Mol Biol. 105(1-5):150-8. MacDonald CJ, Ciolino HP, Yeh GC. (2001) Dibenzoylmethane modulates aryl hydrocarbon receptor function and expression of cytochromes P50 1A1, 1A2, and 1B1. Cancer Res. 61(10):3919-24. Manz A, Berger J, Dwyer JH, Flesch-Janys D, Nagel S, Waltsgott H. (1991) Cancer mortality among workers in chemical plant contaminated with dioxin. Lancet. 338(8773):959-64. Martucci CP, Fishman J. (1993) P450 enzymes of estrogen metabolism. Pharmacol Ther. 57(2-3):237-57. Review. Mobley JA, Bhat AS, Brueggemeier RW. (1999) Measurement of oxidative DNA damage 107 by catechol estrogens and analogues in vitro. Chem Res Toxicol. 12(3):270-7. Nagai M, Conney AH, Zhu BT. (2004) Strong inhibitory effects of common tea catechins and bioflavonoids on the O-methylation of catechol estrogens catalyzed by human liver cytosolic catechol-O-methyltransferase. Drug Metab Dispos. 32(5):497-504. Newbold RR, Liehr JG. (2000) Induction of uterine adenocarcinoma in CD-1 mice by catechol estrogens. Cancer Res. 60(2):235-7. Parkin DM, Bray F, Ferlay J, Pisani P. (2005) Global cancer statistics 2002. CA Cancer J. Clin. 55, 74-108. Parkin DM, Pisani P, Ferlay J. (1993) Estimates of the worldwide incidence of eighteen major cancers in 1985. Int J Cancer. 54(4):594-606. Parl FF, Dawling S, Roodi N, Crooke PS. (2009) Estrogen metabolism and breast cancer: a risk model. Ann N Y Acad Sci. 1155:68-75. Pasqualini JR, Chetrite G, Blacker C, Feinstein MC, Delalonde L, Talbi M, Maloche C. (1996) Concentrations of estrone, estradiol, and estrone sulfate and evaluation of sulfatase and aromatase activities in pre- and postmenopausal breast cancer patients. J Clin Endocrinol Metab. (4):1460-4. Paul, L. and Steven, R. (1990) Protein adducts in the molecular dosimetry of chemical carcinogens. Carcinogen. 11(4),507-518. Phillips DH. (1999) Polycyclic aromatic hydrocarbons in the diet. Mut Res 443(1-2):139–47. Poirier, M.C., Santella, R.M., Weston, A. (2000) Carcinogen macromolecular adducts and their measurement. Carcinogenesis. 21(3), 353-359. Preuss R, Angerer J, Drexler H. (2003) Naphthalene--an environmental and occupational toxicant. Int Arch Occup Environ Health. 76(8):556-76. Preuss, R., Angerer, J and Drexler, H. (2003) Naphthalene-an environmental and occupational toxicant, Int.Arch.Occup. Environ.Health. 76, 556-576. Rappaport, S. M., Ting D., Jin Z., Yeowell-O''Connell K., Waidyanatha S.and McDonald T. (1993) Application of Raney nickel to measure adducts of styrene oxide with hemoglobin and albumin, Chem.Res.Toxicol. 6, 238-244. Rappaport, S.M., Waidyanatha, S., Qu, Q., Shore, R., Jin, X., Cohen, B., Chen, L.C., 108 Melikian, A.A., Li, G., Yin, S., Yan, H., Xu, B., Mu, R., Li, Y., Zhang, X., Li, K. (2002) Albumin Adducts of Benzene Oxide and 1,4-Benzoquinone as Measures of Human Benzene Metabolism. Cancer Research. 62, 1330-1337. Rappaport, S.M., Waidyanatha, S., Serdar, B. (2004) Naphthalene and its Biomarkers as Measures of Occupational Exposure to Polycyclic Aromatic Hydrocarbons. J. Environ. Monit. 6,413-416. Revich B, Aksel E, Ushakova T, Ivanova I, Zhuchenko N, Klyuev N, Brodsky B, Sotskov Y. (2001) Dioxin exposure and public health in Chapaevsk, Russia. Chemosphere. 43(4-7):951-66. Rogan EG, Badawi AF, Devanesan PD, Meza JL, Edney JA, West WW, Higginbotham SM, Cavalieri EL. (2003) Relative imbalances in estrogen metabolism and conjugation in breast tissue of women with carcinoma: potential biomarkers of susceptibility to cancer. Carcinogenesis. 24(4):697-702. Rogan, E.G., Badawi, A.F., Devanesan, P.D., Meza, J.L., Edney, J.A., West, W. W., Higginbotham, S.M., Cavalieri, E.L. (2003) Relative imbalances in estrogen metabolism and conjugation in breast tissue of women with carcinoma: potential biomarkers of susceptibility to cancer. Carcinogenesis. 24(4), 697-702. Rundle A, Tang D, Hibshoosh H, Estabrook A, Schnabel F, Cao W, Grumet S, Perera FP. (2000) The relationship between genetic damage from polycyclic aromatic hydrocarbons in breast tissue and breast cancer. Carcinogenesis. 21(7):1281-9. Russo J, Hasan Lareef M, Balogh G, Guo S, Russo IH. (2003) Estrogen and its metabolites are carcinogenic agents in human breast epithelial cells. J Steroid Biochem Mol Biol. 87(1):1-25. Review. Russo J, Lareef MH, Tahin Q, Hu YF, Slater C, Ao X, Russo IH. (2002) 17Beta-estradiol is carcinogenic in human breast epithelial cells. J Steroid Biochem Mol Biol. 80(2):149-62. Russo, J., Hu, Y. F., Tahin, Q., Mihaila, D., Slater, C., Lareef, M. H., and Russo, I. H. (2001) Carcinogenicity of estrogens in human breast epithelial cells. APMIS 109,39-52. Saeed M, Zahid M, Gunselman SJ, Rogan E, Cavalieri E. (2005) Slow loss of deoxyribose from the N7deoxyguanosine adducts of estradiol-3,4-quinone and hexestrol-3'',4''-quinone. Implications for mutagenic activity. Steroids. 70(1):29-35. 109 Safe SH, Zacharewski T. (1997) Organochlorine exposure and risk for breast cancer. Prog Clin Biol Res. 396:133-45. Safe, S., Wormke, M., Samudio, I. (2000) Mechanisms of Inhibitory Aryl Hydrocarbon Receptor-Estrogen Receptor Crosstalk in Human Breast Cancer Cells. J. Mammary Gland Biol. Neoplasia. 5,295-306. Shen YC, Chang CJ, Hsu C, Cheng CC, Chiu CF, Cheng AL. (2005) Significant difference in the trends of female breast cancer incidence between Taiwanese and Caucasian Americans: implications from age-period-cohort analysis. Cancer Epidemiol Biomarkers Prev. 14(8):1986-90. Shimizu Y, Nakatsuru Y, Ichinose M, Takahashi Y, Kume H, Mimura J, Fujii-Kuriyama Y, Ishikawa T. (2000) Benzo[a]pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor. Proc Natl Acad Sci U S A. Shin HR, Boniol M, Joubert C, Hery C, Haukka J, Autier P, Nishino Y, Sobue T, Chen CJ, You SL, Ahn SH, Jung KW, Law SC, Mang O, Chia KS. (2010) Secular trends in breast cancer mortality in five East Asian populations: Hong Kong, Japan, Korea, Singapore and Taiwan. Cancer Sci. (2010)101(5):1241-6. Skupinska K, Misiewicz I, Kasprzycka-Guttman T. (2004) Polycyclic aromatic hydrocarbons: physiochemical properties, environmental appearance and impact on living organisms. Acta Pol Pharm 61(3):233–40. Spink DC, Eugster HP, Lincoln DW 2nd, Schuetz JD, Schuetz EG, Johnson JA, Kaminsky LS, Gierthy JF. (1998) 17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1A1: a comparison of the activities induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in MCF-7 cells with those from heterologous expression of the cDNA. Arch Biochem Biophys. 293(2):342-8. Stelck RL, Baker GL, Sutherland KM, Van Winkle LS. (2005) Estrous cycle alters naphthalene metabolism in female mouse airways. Drug Metab Dispos. 33(11):1597-602. Ten Tusscher, G. W., Steerenberg, P. A., van Loveren, H., Vos, J. G., von dem Borne, A.E., Westra, M., van der Slikke, J. W., Olie, K., Pluim, H. J., and Koppe, J. G. (2003) Persistent hematologic and immunologic disturbances in 8-year-old Dutch children associated with perinatal dioxin exposure. Environ Health Perspect. 111,1519-23. Tiernan, T. O., Taylor, M. L., Garrett, J. H., VanNess, G. F., Solch, J. G., Wagel, D. 110 J.,Ferguson, G. L., and Schecter, A. (1985) Sources and fate of polychlorinated Tornqvist, M., Fred, C., Hanglund, J., Helleberg, H., Paulsson, B., Rydberg, P. (2002) Protein adducts: quantitative and qualitative aspects of their formation, analysis and applications. Journal of Chromatography B. 778, 279-308. Tornqvist, M., Mowrer, J., Jensen, S. and Ehrenberg, L. (1986) Monitoring of environmental cancer initiators through hemoglobin adducts by a modifiedEdman degradation method. Analytical Biochemistry. 154,255-266. Usmani KA, Usmani TM, Rose RL, Hodgson E. (2006) Inhibition of the human liver microsomal and human cytochrome P450 1A2 and 3A4 metabolism of estradiol by deployment-related and other chemicals. Drug Metab Dispos. 34(9):1606-14. Valdez KE, Shi Z, Ting AY, Petroff BK. (2009) Effect of chronic exposure to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin in female rats on ovarian gene expression. Reprod Toxicol. 28(1):32-7. Van Voorhis BJ, Dawson JD, Stovall DW, Sparks AE, Syrop CH. (1996) The effects of smoking on ovarian function and fertility during assisted reproduction cycles. Obstet Gynecol. 88(5):785-91. Veglia F, Matullo G, Vineis P. (2003) Bulky DNA adducts and risk of cancer: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 12(2):157-60. Review. Waidyanatha, S., Rappaport, S.M., (2008) Hemoglobin and albumin adducts of naphthalene-1,2-oxide, 1,2-naphthoquinone and 1,4-naphthoquinone in Swiss Webster mice. Chemico-Biological Interactions. 172,105-114. Waidyanatha, S., Troester, M.A., Lindstrom, A.B. (2002) Measurement of Hemoglobin and Albumin Adducts of Naphthalene-1,2-Oxide, 1,2-Naphthoquinone and 1,4-Naphthoquinone After Administration of Naphthalene to F344 Rats. Chem. Biol. Interact. 141,189-210. Waidyanatha, S., Zheng, Y., Serdar, B. (2004) Albumin Adducts of Naphthalene Metabolites as Biomarkers of Exposure to Polycyclic Aromatic Hydrocarbons. Cancer Epidemiol. Biomarkers Prev. 13,117-124. Wang, S.L., Chang, Y.C., Chao, H.R. (2006) Body Burdens of Polychlorinated Dibenzo-p-Dioxins, Dibenzofurans, and Biphenyls and their Relations to Estrogen Metabolism in Pregnant Women. Environ. Health Perspect. 114, 740-745. 111 Warner, M., Eskenazi, B., Mocarelli, P. (2002). Serum Dioxin Concentrations and Breast Cancer Risk in the Seveso Women''s Health Study. Environ. Health Perspect. 110,625-628. Westhoff C, Gentile G, Lee J, Zacur H, Helbig D. (1996) Predictors of ovarian steroid secretion in reproductive-age women. Am J Epidemiol. 144(4):381-8. Whitlock JP Jr. (1999) Induction of cytochrome P4501A1. Annu Rev Pharmacol Toxicol. 39:103-25. Review. Yager JD, Davidson NE. (2006) Estrogen carcinogenesis in breast cancer. N Engl J Med. 354(3):270-82. Review. Yang, Hsi-Hsien., Jung, Ray-chen., Wang, Ya-Fen. (2005b) Polycyclic Aromatic Hydrocarbon Emissions from Joss Paper Furnaces. Atmospheric Environment. 39,3305-3312. Zahid M, Kohli E, Saeed M, Rogan E, Cavalieri E. (2005) The greater reactivity of estradiol-3,4-quinone vs estradiol-2,3-quinone with DNA in the formation of depurinating adducts: implications for tumor-initiating activity. Chem Res Toxicol. 19(1):164-72. Zhang L, Weddle DL, Thomas PE, Zheng B, Castonguay A, Schuller HM, Miller MS. (2000) Low levels of expression of cytochromes P-450 in normal and cancerous fetal pancreatic tissues of hamsters treated with NNK and/or ethanol. Toxicol Sci. 56(2):313-23. Zhao Z, Kosinska W, Khmelnitsky M, Cavalieri EL, Rogan EG, Chakravarti D, Sacks PG, Guttenplan JB. Mutagenic activity of 4-hydroxyestradiol, but not 2-hydroxyestradiol, in BB rat2 embryonic cells, and the mutational spectrum of 4-hydroxyestradiol. Chem Res Toxicol. 19(3):475-9. Zhu BT, Conney AH. (1998) Functional role of estrogen metabolism in target cells: review and perspectives. Carcinogenesis. 19(1):1-27. Review. Zmirou D, Masclet P, Boudet C, Dor F, Dechenaux J. (2000) Personal exposure to atmospheric polycyclic aromatic hydrocarbons in a general adult population and lung cancer risk assessment. J Occup Environ Med 42:121–6.
摘要: 本研究之主旨係運用蛋白質胼合物(protein adduct)作為生物指標 (biomarker),以雌性激素及萘之醌類化物與蛋白質形成之共價鍵結產物-蛋白質胼合物,作為推估 雌性激素及萘之醌類化物於標的器官之組織劑量。並探討於多環芳香族碳氫化合物(Polycyclic aromatic hydrocarbons, PAHs)及影響雌性激素代謝活化之干擾物質,例如戴奧辛(2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD)之環境暴露下,對萘及雌性激素醌 類化物與蛋白質反應形成蛋白質胼合物之影響。本研究係以TFAA (trifluoroacetic acid anhydride)作為衍生劑,並於強酸環境下移除雌性激素及萘之醌類化物與蛋白質上cysteine之硫原子鍵結產生之胼合物,並經由溶劑萃取濃縮,再利用氣相層析負離子化學離子化質譜儀(GC/NICI/MS),進行定性分析。此外運用高效能液相層析儀純化雌性激素及萘之醌類化物與N-acetyl-L-cysteine反應形成之胼合物,以製備定量所需之標準品;同時利用同位素內標準品,對待測物進行定性及定量分析。實驗結果分別敘述如下 (1)在濃度效應實驗結果顯示,其具有線性正關係,隨著每添加1nM之estrogen-2,3-quinones (E2-2,3-Q)會增加13.4及29.0pmole/g之2-hydroxyestradiol-1-albumin (2-OHE2-1-Alb) 及2-hydroxyestradiol -4-albumin (2-OHE2-4-Alb),而每添加1nM之estrogen-2,3-quinones (E2-2,3-Q)會增加109.5 pmole/g 之4-hydroxyestradiol-2-albumin (4-OHE2-2-Alb)之形成。而在時間效應實驗結果顯示E2-2,3-Q及E2-3,4-Q在十分鐘即達到最大鍵結量,而隨著時間加長並沒有顯著之差異 (2) 在人類乳癌細胞MCF-7以TCDD 預處理(10 nM, 72小時)後,添加雌性激素(10-1000 nM, 9小時),及共同添加COMT抑制劑(Ro41-0960)實驗中,添加COMT抑制劑會相較於單獨暴露雌性激素增加兩倍之雌性激素醌類蛋白質胼合物。 (3)A/J mice動物實驗測試分析結果,同時暴露TCDD+NNK會增加雌性激素醌類蛋白質胼合物之生成。 (4)乳癌病患之血清白蛋白分析結果中,測得萘醌類化物蛋白質胼合物之背景值,1,2-naphthoquinone (1,2-NPQ)及1,4-naphthoquinone (1,4-NPQ)分別為167-653及19.8-68.6 pmol/g。此外,在雌性激素醌類蛋白質胼合物之分析結果顯示,乳癌病患測得雌性激素醌類之蛋白質胼合物2-OHE2-1-Alb、2-OHE2-4-Alb及4-OHE2-2-Alb分別為ND(Not Detection)-183,115-1097及433-1436 pmol/g。此一結果顯示,乳癌病患相 較於正常人之控制組,其4-OHE2-Alb 之背景值約高出2-4倍。 本研究預期此一蛋白質胼合物分析法,將能作為一高效率之生物指標,提供流行病學中評估PAHs 及雌性激素代謝活化之干擾物質長期暴露族群之研究。
The objective of this research is to develop a biochemical assay using protein adducts as biomarker of environmental exposure to polycyclic aromatic hydrocarbons (PAHs) and modulators of estrogen homeostasis, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). This methodology ultilizes trifluoroacetic acid (TFAA) and methanesulfonic acid (MSA) as catalysts to cleave cysteinyl adducts of naphthalene- and estrogen-derived quinones on proteins. The cleaved adducts are recovered by organic solvent extractions and analyzed by gas chromatography- negative-ion-chemical-ionization-mass spectrometer (GC-NICI-MS). The isomeric forms of cysteinyl adducts of naphthoquinones, including 1,2-naphthoquinone (1,2-NPQ) and 1,4-naphthoquinone (1,4-NPQ) as well as estrogen quinones, including estrogen-2,3-quinones (E2-2,3-Q) and estrogen-3,4-quinones (E2-3,4-Q), are characterized by using isotopically-labelled bound internal standards after adducts cleavage by the TFAA/MSA derivatization procedure. Results were summarized as follows: (1) Results form in vitro experiments confirmed that the production of estrogen quinone-derived adducts on serum Alb increased with increased concentration of estrogen quinones (0-100 nM). Linear relationships were observed over the range of concentration. The average formation of estrogen quinone-derived cysteinyl adducts per unit concentration of estrogen quinones was estimated to be 13.4, 29.0 , and 109.5 (pmol/g Alb)/(nM) for 2-hydroxyestradiol-1-albumin, 2-hydroxyestradiol-4-albumin, and 4-hydroxyestradiol-2-albumin, respectively. Time-course experiments suggested that both E2-2,3-Q- and E2-3,4-Q-derived adducts rapidly reached maximum values at 5 min mark and remained constant thereafter. (2) In human MCF-7 breast cancer cells, with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) pretreatment (10 nM for 72 h), production of estrogen quinone-derived protein adducts was detected in cells exposed to estrogen (10 - 1000 nM for 9 h). Co-treatment of Ro 41-0960, a catechol-o-methyl transferase (COMT) inhibitor, further the production of estrogen quinone-derived adducts in Co-treatment of Ro 41-0960 was 2-fold higher than exposed estrogen only. (3) Results from the animal study showed that Co-treatment of TCDD and Nicotine-derived nitrosamine ketone (NNK) enhanced the production of estrogen quinone-derived adducts on hemoglobin derived from A/J mice. (4) Results from the analysis of human serum albumin indicated that the background levels of cysteinyl adducts of 1,2-NPQ and 1,4-NPQ on human serum albumin derived from breast cancer patients in at levels ranging from 167-653 and 19.8-68.6 pmol/g, respectively. In addition, cysteinyl adducts of 2-OHE2-1-Alb, 2-OHE2-4-Alb and 4-OHE2-2-Alb were detected at levels ranging from ND-183, 115-1097 and 433-1436 pmol/g, respectively. Additionally, these finding indicated that levels of 4-OHE2-2-Alb in breast cancer patients were ~2-4 fold greater than healthy controls. Overall, we concluded that the methodology developed in this study may be applied to epidemiological study to serve as biomarkers of environmental exposure to PAHs and other modulators of estrogen homeostasis.
其他識別: U0005-2607201016425300
Appears in Collections:環境工程學系所



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.