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研究生:林晏瑜
研究生(外文):Lin, Yen Yu
論文名稱:細胞色素3A4外顯子在中國人的遺傳多型性研究
論文名稱(外文):Genetic polymorphism of CYP3A4 exons in Chinese
指導教授:黃金鼎黃金鼎引用關係
指導教授(外文):Huang, Jin Ding
學位類別:碩士
校院名稱:國立成功大學
系所名稱:藥理學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:1999
畢業學年度:87
語文別:中文
論文頁數:89
中文關鍵詞:細胞色素細胞色素3A4多型性
外文關鍵詞:CYPCYP3A4polymorphism
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中文摘要
細胞色素P450大家族為含血基質硫醇酸類蛋白,負責大部分藥物的氧化代謝作用。多數環境中的化合物屬於致癌性物質及突變原,在受到P450連結的單氧化酵素系統代謝後會被活化。到目前為止,發現至少有超過481種基因型的細胞色素P450大家族存在真核生物(包含動植物)及原核生物中。在P450家族中CYP3A是存在人類肝臟中的P450最主要的型態。在人類CYP3A位在第七對染色體上,且至少包含三種基因型-CYP3A3/4、 CYP3A5、 CYP3A 7。
從1989年CYP3A4被發現後,它被認為是重要的藥物代謝酵素。主要存在肝臟中,約佔30%的P450含量,促成約60%藥物的氧化代謝作用,包括免疫抑制劑、鈣離子管道阻斷劑、癌症化學治療劑、 抗組織胺、 鎮靜劑及合成的雌性素。CYP3A4也被發現富含在腸道上皮,因此口服CYP3A4的受質,在吸收前即受到明顯的肝臟外代謝作用。CYP3A4可催化各種類固醇及外生性物質的氧化作用,平均女性大於男性(24%)且其表現可被誘導。
除抑制及誘導作用外,微粒體對藥物的代謝作用可被其他因素所影響,包括:基因多型性、年齡、營養、肝臟疾病及內生性物質。基因多型性的影響會導致族群中部分人口降低、缺乏或增加特定反應的活性。先前的研究作者發現,從個體接受CYP3A4的誘導劑後,會使CYP3A的表現量約達人類肝臟全部P450的一半,而其中微粒體含的CYP3A4的個體差異將近60倍,而關於此點仍無基因多型性的證據。
先前的研究已從成人肝臟cDNA基因庫分離出CYP3A3(P-450HLp) 、 CYP3A4(NF10、 NF25 and hPCN1) 及 CYP3A5 (hPCN3 and HLp2),以及從胎兒肝臟cDNA基因庫分離出CYP3A7 (HFL33)的cDNA複製密碼。目前從三種基因組複製的CYP3A4已得知:包括全部的外顯子、 外顯子-內含子的接合處及5¢端從轉錄起點至核酸-1105位區域位置的基因序列。在本篇研究中,各分析了100及168個中國人的基因序列。我們利用PCR-SSCP及PCR direct-sequence的方法, 研究在CYP3A4 exon3、 4 、5、 6、9、13的基因多型性,及利用限制片段多型性的方法,去證實在CYP3A4的突變位置。
我們發現在168個受試者中,有5位其CYP3A4基因中的第455位置 (位於 exon5上) 有點突變發生,即由A455突變成A455/G455,此變化造成氨基酸由Ile118變成Ile118/Val118。另外在CYP3A4基因中,第934位置(位於 exon9上)也有突變發生,即單一對偶質(allele)嵌入A934一個氮鹼基,此造成基因轉譯提前結束及蛋白質合成缺失。而這兩種類型的突變及其造成的影響,尚未有文獻報導。對於CYP3A4在exon5及exon9的基因多型性,可能會影響到個體對於代謝CYP3A4受質的感受性,我們進一步研究CYP3A4的酵素代謝活性:收集受試者早晨尿液檢體,分別利用enzyme-linked immunosorbent assay (ELISA)及 enzyme-linked fluorescent assay (ELFA) 的方法分析尿液中6β- hydroxycortisol (6β-OHF)及free cortisol (F) 的含量。我們的結果顯示:在台灣的中國人具變異型基因A455/G455 及單一對偶質嵌入 A934 的變異型,比較正常態基因的人,其CYP3A4酵素代謝活性會降低,此結果反映在6β-OHF/F的比值上。
Abstract
The superfamily of heme-thiolate proteins knows as the cytochromes P450 is responsible for the oxidative metabolism of the majority of drugs. And most enviromental chemicals are carcinogenic and mutagenic only after undergoing metabolic activation by a P450-linked monooxygenase system. The cytochrome P450 superfamily is composed of at least 481 genes found in eukaryotes (both plants and animals) and prokaryotes. Among the families of P450, CYP3A is one of the major forms of P450 in human livers. In human, the CYP3A locus positioned on chromosome 7 has at least three genes including CYP3A4/3 (CYP3A3 is believed to be an allelic variant of CYP3A4), CYP3A5 and CYP3A7.
Since 1989, CYP3A4 has emerged as a major drug-metabolizing enzyme, it accounts for approximately 30% of the P450 content in the liver and mediates almost 60% of drug oxidation, including immunosuppressants, calcium channel blockers, cancer chemotherapeutic agents, antihistaminics, sedatives, and synthetic estrogens. It is also found in substantial amounts in the gut epithelium; thus, orally administered substrates of CYP3A4 undergo significant extrahepatic metabolism before absorption. This enzyme catalyzes the oxidation of various steroids and xenobiotics, the same enzyme is also capable of activating various promutagens to mutagens. CYP3A4 is present in greater amounts (24%) in women as compared to men and is inducible at mRNA and protein levels in the liver and intestine.
In addition to inhibition and induction, microsomal drug metabolism is affected by genetic polymorphisms, age, nutrition, hepatic disease and endogenous chemicals. Genetic polymorphisms lead to subpopulations of patients with decreased, absent, or even increased activities of certain reactions. The levels of CYP3A4 vary by as much as 60-fold between human liver microsome samples with the levels of CYP3A forms approaching 50% of the total cytochrome P450 present in human liver samples from individuals receiving inducers of CYP3A4, but there is no evidence of genetic polymorphism. The full impact of the CYP3A4 polymorphism has yet to be fully appreciated.
cDNA clone codings for CYP3A3 (P-450HLp), CYP3A4 (NF10, NF25 and hPCN1) and CYP3A5 (hPCN3 and HLp2) was isolated from adult liver cDNA libraries, and CYP3A7 (HFL33) from fetal liver cDNA libraries. The sequence of three genomic clones for CYP3A4 were analyzed for all exons, exon-intron junctions and the 5’-flanking region from the major transcription site to nucleotide position -1105. (Hashimoto et al., 1993) The sequence of CYP3A4 gene of 100 or 168 Chinese subjects has been analyzed in this study. With PCR-SSCP (single strand conformation polymorphism) and PCR direct-sequencing method, polymorphism at exon 3, 4, 5, 6, 9, 13 were investigated, and developed endonuclease digestion methods to determine the genetic characteristics of the CYP3A4 gene in a Chinese population.
We found five of 336 alleles showed a heterozygous adenine at 455 base pairs (A455) to guanine (G455) mutation (Ile118 to Val118) in exon 5. And one of 336 alleles showed a heterozygous adenine at 934 base pairs (A934) insertion, produced early stop codon and protein synthesize damage. The clinical consequence of these mutation has not been addressed in the literature. The polymorphism of exon 5 and exon 9 of CYP3A4 may influence individual susceptibility to metabolism of CYP3A4 substrate.
We investigated CYP3A4 activity, morning spot urine samples were collected for measurement of 6β- hydroxycorticol (6β-OHF) and free cortisol (F) by an enzyme- linked immunosorbent assay (ELISA) and an enzyme-linked fluorescent assay (ELFA), respectively. Our result show both decrease in CYP3A4 enzyme activity, reflected as both decrease in the 6β-OHF/F ratio, in Taiwan Chinese with A455/G455 and A934 insertion of one allele compared with those wild type.
Futher investigation is needed to clarify the significance and the genetic polymorphism in the human CYP3A4 metabolism of drug substrates.
目錄
中文摘要.................................................................. 1
英文摘要.................................................................. 3
第一章緒論...............................................................6
第二章 實驗材料、儀器及方法..........................13
第一節 實驗材料....................................................13
第二節 實驗儀器....................................................18
第三節 實驗方法....................................................20
第三章實驗結果.....................................................31
第四章討論..............................................................37
參考文獻..................................................................42
圖表...........................................................................53
附錄...........................................................................87
參考文獻:
Aoyama, T., Yamano, S., Waxman, D. J., Lapenson, D. P., Meyer, U. A., Fischer, V., Tyndale, R., Inaba, T., Kalow, W., Gelboin, H. V. & Gonzalez, F. J. Cytochrome P-450 hPCN3, a novel cytochrome P-450 IIIA gene product that is differentially expressed in adult human liver. cDNA and deduced amino acid sequence and distinct specificities of cDNA-expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and cyclosporine. J. Biol. Chem. 1989: 264, 10388-10395.
Beato, M. Gene regulation by steroid hormones. Cell 1989: 56, 335-44.
Beaune, P. H., Umbenhauer, D. R., Bork, R. W., Lloyd, R. S., Guengerich, F. P. Isolation and sequence determination of a cDNA clone related to human cytochrome P-450 nifedipine oxidase. Proc. Natl. Acad. Sci. U S A 1986: 83, 8064-8068.
Bork, R. W., Muto, T., Beaune, P. H., Srivastava, P. K., Lloyd, R. S., Guengerich, F. P. Characterization of mRNA species related to human liver cytochrome P-450 nifedipine oxidase and the regulation of catalytic activity. J. Biol. Chem. 1989: 264, 910-919.
Branch, R. A., Chern, H. D., Adedoyin, A., Romkes-Sparks, M., Lesnick, T. G., Persad, R., Wilkinson, G.R., Fleming, C. M., Dickinson, A. J., Sibley, G. et al. The procarcinogen hypothesis for bladder cancer: activities of individual drug metabolizing enzymes as risk factors. Pharmacogenetics 1995: 5, S97-102.
Broly, F., Marez, D., Sabbagh, N., Legrand, M., Millecamps, S., Lo Guidice, J. M., Boone, P., Meyer, U. A. An efficient strategy for detection of known and new mutations of the CYP2D6 gene using single strand conformation polymorphism analysis. Pharmacogenetics 1995: 5, 373-384.
Chiu, R., Imagawa, M., Imbra, R. J., Bockoven, J. R., Karin, M. Multiple cis- and trans-acting elements mediate the transcriptional response to phorbol esters. Nature 1987: 329, 648-51.
Chodosh, L. A., Baldwin, A. S., Carthew, R. W., Sharp, P. A. Human CCAAT-binding proteins have heterologous subunits. Cell 1988: 53, 11-24.
Cholerton, S., Daly, A. K., Idle, J. R. The role of individual human cytochromes P450 in drug metabolism and clinical response. Trends Pharmacol. Sci. 1992: 13, 434-439.
Coon, M. J., Ding, X. X., Pernecky, S. J., Vaz, A. D. Cytochrome P450: progress and predictions. FASEB J. 1992: 6, 669-673.
Daujat, M., Pichard, L., Fabre, I., Diaz, D., Maurice, M., Pineau, T., Blanc, P., Fabre, G., Fabre, J. M., Saint Aubert, B., and Maurel, P., 1990, Human P450IA and IIIA Subfamilies: Regulation of expression and inducibility in primary cultures of human hepatocytes, in: Drug Metabolizing Enzymes: Genetics, Regulation and Toxicology, Proceedings of the Eighth International Symposium on Microsomes and Drug Oxidations (Stockholm, June 25-29) (M. Ingelman-Sundberg, J.-A. Gustafsson, and S. Orrenius, eds.), p. 16.
Degawa, M., Stern, S. J., Martin, M. V., Guengerich, F. P., Fu, P. P., Ilett, K. F., Kaderlik, R. K., Kadlubar, F. F. Metabolic activation and carcinogen-DNA adduct detectionin human larynx. Cancer Res. 1994: 54, 4915-9.
Domanski, T. L., Liu, J., Harlow, G. R., Halpert, J. R. Analysis of four residues within substrate recognition site 4 of human cytochrome P450 3A4: role in steroid hydroxylase activity and alpha-naphthoflavone stimulation. Arch. Biochem. Biophys. 1998 : 350, 223-32.
de Morais, S. M., Wilkinson, G. R., Blaisdell, J., Nakamura, K., Meyer, U. A., Goldstein, J. A. The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J. Biol. Chem. 1994: 269, 15419-15422.
Felix, C. A., Walker, A. H., Lange, B. J., Williams, T. M., Winick, N. J., Cheung, N. K., Lovett, B. D., Nowell, P. C., Blair, I. A., Rebbeck, T. R. Association of CYP3A4 genotype with treatment-related leukemia. Proc. Natl. Acad. Sci. U S A 1998: 95, 13176-13181.
Fujii-Kuriyama, Y., Imataka, H., Sogawa, K., Yasumoto, K., Kikuchi, Y. Regulation of CYP1A1 expression. FASEB J. 1992: 6, 706-10.
Fulco, A. J. P450BM-3 and other inducible bacterial P450 cytochromes: biochemistry and regulation. Annu. Rev. Pharmacol. Toxicol. 1991: 31, 177-203.
Ged, C., Rouillon, J. M., Pichard, L., Combalbert, J., Bressot, N., Bories, P., Michel, H., Beaune, P., Maurel, P. The increase in urinary excretion of 6 beta-hydroxycortisol as a marker of human hepatic cytochrome P450IIIA induction. Br. J. Clin. Pharmacol. 1989: 28, 373-387.
Gonzalez, F. J., Schmid, B. J., Umeno, M., Mcbride, O. W., Hardwick, J. P., Meyer, U. A., Gelboin, H. V., Idle, J. R. Human P450PCN1: sequence, chromosome localization, and direct evidence through cDNA expression that P450PCN1 is nifedipine oxidase. DNA 1988: 7, 79-86.
Guengerich, F. P., Martin, M. V., Beaune, P. H., Kremers, P., Wolff, T., Waxman, D. J. Characterization of rat and human liver microsomal cytochrome P-450 forms involved in nifedipine oxidation, a prototype for genetic polymorphism in oxidative drug metabolism. J. Biol. Chem. 1986: 261, 5051-5060.
Guengerich, F. P. Oxidation of 17 alpha-ethynylestradiol by human liver cytochrome P-450. Mol. Pharmacol. 1988: 33, 500-508.
Guengerich, F. P. Mechanism-based inactivation of human liver microsomal cytochrome P-450 IIIA4 by gestodene. Chem. Res. Toxicol. 1990: 3, 363-371.
Guengerich, F. P., Gillam, E. M. J., Martin, M. V., Baba, T., Kim, B. R., Shimada, T., Raney, K. D., and Yun, C. H., 1994, The importance of cytochrome P450 3A enzymes in drug metabolism, in: Schering Foundation Workshop, Assessment of the Use of Single Cytochrome P450 Enzymes In Drug Research (March 23-25, Springer-Verlag Berlin), pp 161-186.
Guengerich, F. P. Human cytochromes P450. In P. R. Ortiz de Montellano (ed.), Cytochromes P450: Structure, Mechanism, and Biochemistry, Plenum Press, New York, 1995, pp. 473-535.
Guengerich, F. P. Cytochrome P-450 3A4: regulation and role in drug metabolism. Annu. Rev. Pharmacol. Toxicol. 1999: 39, 1-17.
Hashimoto, H., Toide, K., Kitamura, R., Fujita, M., Tagawa, S., Itoh, S., Kamataki, T. Gene structure of CYP3A4, an adult-specific form of cytochrome P450 in human livers, and its transcriptional control. Eur. J. Biochem. 1993: 218, 585-595.
He, Y. A., He, Y. Q., Szklarz, G. D., Halpert, J. R. Identification of three key residues in substrate recognition site 5 of human cytochrome P450 3A4 by cassette and site-directed mutagenesis. Biochemistry 1997: 36, 8831-9.
Hunt, C. M., Westerkam, W. R., Stave, G. M. Effect of age and gender on the activity of human hepatic CYP3A. Biochem. Pharmacol. 1992: 44, 275-283.
Imataka, H., Sogawa, K., Yasumoto, K., Kikuchi, Y., Sasano, K., Kobayashi, A., Hayami, M., Fujii-Kuriyama, Y. Two regulatory proteins that bind to the basic transcription element (BTE), a GC box sequence in the promoter region of the rat P-4501A1 gene. EMBO J. 1992: 11, 3663-71.
Johansson, I., Yue, Q.Y., Dahl, M. L., Heim, M., Sawe, J., Bertilsson, L., Meyer, U. A., Sjoqvist, F., Ingelman-Sundberg, M. Genetic analysis of the interethnic difference between Chinese and Caucasians in the polymorphic metabolism of debrisoquine and codeine. Eur. J. Clin. Pharmacol. 1991: 40, 553-6.
Kalow, W., Goedde, H. W. and Agarwal, D. P. Ethnic Differences in Reactions to Drugs and Xenobiotics, AR Liss, New York, 1986.
Kaminsky, L. S., Fasco, M. J. Small intestinal cytochromes P450. Crit. Rev. Toxicol. 1991: 21, 407-422.
Kelly, J. D., Eaton, D. L., Guengerich, F. P., Coulombe, R. A., Jr. Aflatoxin B1 activation in human lung. Toxicol. Appl. Pharmacol. 1997: 144, 88-95.
Kitada, M., Kamataki, T. Partial purification and properties of cytochrome P450 from homogenates of human fetal livers. Biochem. Pharmacol. 1979: 28, 793-797.
Kitada, M., Kamataki, T., Itahashi, K., Rikihisa, T., Kanakubo, Y. P-450 HFLa, a form of cytochrome P-450 purified from human fetal livers, is the 16 alpha-hydroxylase of dehydroepiandrosterone 3-sulfate. J. Biol. Chem. 1987: 262, 13534-13537.
Kolars, J., Schmiedelin-Ren, P., Dobbins, W., Merion, R., Wrighton, S., and Watkins, P. Heterogeneity of P-450 IIIA expression in human gut epithelia. FASEB J. 1990: 4, A2242.
Kolars, J. C., Awni, W. M., Merion, R. M., Watkins, P. B. First-pass metabolism of cyclosporin by the gut. Lancet 1991: 338, 1488-1490.
Komori, M., Hashizume, T., Ohi, H., Miura, T., Kitada, M., Nagashima, K., Kamataki, T. Cytochrome P-450 in human liver microsomes: high-performance liquid chromatographic isolation of three forms and their characterization. J. Biochem. (Tokyo) 1988: 104, 912-916.
Komori, M., Nishio, K., Ohi, H., Kitada, M., Kamataki, T. Molecular cloning and sequence analysis of cDNA containing the entire coding region for human fetal liver cytochrome P-450. J. Biochem. (Tokyo) 1989: 105, 161-163.
Komori, M., Nishio, K., Fujitani, T., Ohi, H., Kitada, M., Mima, S., Itahashi, K., Kamataki, T. Isolation of a new human fetal liver cytochrome P450 cDNA clone: evidence for expression of a limited number of forms of cytochrome P450 in human fetal livers. Arch. Biochem. Biophys. 1989: 272, 219-225.
Lai, C., Shields, P. G. The role of interindividual variation in human carcinogenesis. J. Nutr. 1999: 129 (2S Suppl), 552S-555S.
Lehmann, J. M., McKee, D. D., Watson, M. A., Willson, T. M., Moore, J. T., Kliewer, S. A. The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions. J. Clin. Invest. 1998: 102, 1016-1023.
Lin, Y., Anderson, G. D., Kantor, E., Ojemann, L. M., Wilensky, A. J. Differences in the urinary excretion of 6-beta-hydroxycortisol/cortisol between Asian and Caucasian women. J. Clin. Pharmacol. 1999: 39, 578-82.
Lytton, S. D., Helander, A., Zhang-Gouillon, Z. Q., Stokkeland, K., Bordone, R., Arico, S., Albano, E., French, S. W., Ingelman-Sundberg, M. Autoantibodies against cytochromes P-4502E1 and P-4503A in alcoholics. Mol. Pharmacol. 1999: 55, 223-33.
Marez, D., Legrand, M., Sabbagh, N., Guidice, J. M., Spire, C., Lafitte, J. J., Meyer, U. A., Broly, F. Polymorphism of the cytochrome P450 CYP2D6 gene in a European population: characterization of 48 mutations and 53 alleles, their frequencies and evolution. Pharmacogenetics 1997: 7, 193-202.
Meyer, U. A. Overview of enzymes of drug metabolism. J. Pharmacokinet. Biopharm. 1996: 24, 449-59.
Molowa, D. T., Schuetz, E. G., Wrighton, S. A., Watkins, P. B., Kremers, P., Mendez-Picon, G., Parker, G. A., Guzelian, P. S. Complete cDNA sequence of a cytochrome P-450 inducible by glucocorticoids in human liver. Proc. Natl. Acad. Sci. U S A 1986: 83, 5311-5315.
Morel, F., Beaune, P. H., Ratanasavanh, D., Flinois, J. P., Yang, C. S., Guengerich, F. P., Guillouzo, A. Expression of cytochrome P-450 enzymes in cultured human hepatocytes. Eur. J. Biochem. 1990: 191, 437-444.
Muntane-Relat, J., Ourlin, J. C., Domergue, J., Maurel, P. Differential effects of cytokines on the inducible expression of CYP1A1, CYP1A2, and CYP3A4 in human hepatocytes in primary culture. Hepatology 1995: 22, 1143-1153.
Murray, G. I., McFadyen, M. C., Mitchell, R. T., Cheung, Y. L., Kerr, A. C., Melvin, W. T. Cytochrome P450 CYP3A in human renal cell cancer. Br. J. Cancer 1999: 79, 1836-1842.
Nelson, D. R., Kamataki, T., Waxman, D. J., Guengerich, F. P., Estabrook, R.W., Feyereisen, R., Gonzalez, F. J., Coon, M. J., Gunsalus, I. C., Gotoh, O., Okuda, K., and Nebert, D. W. The P450 superfamily: update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature. DNA Cell Biol. 1993: 12, 1-51.
Nelson, D. R., Koymans, L., Kamataki, T., Stegeman, J. J., Feyereisen, R., Waxman, D. J., Waterman, M. R., Gotoh, O., Coon, M. J., Estabrook, R. W., Gunsalus, I. C., Nebert, D. W. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 1996: 6, 1-42.
Ng, M. C., Young, R. P., Critchley, J. A., Leung, N. W., Lau, J. W., Li, A. K. Urinary 6 beta-hydroxycortisol excretion in Hong Kong Chinese patients with hepatocellular carcinoma and other chronic liver diseases. Cancer 1996: 77, 1427-1433.
Ourlin, J. C., Jounaidi, Y., Maurel, P., Vilarem, M. J. Role of the liver-enriched transcription factors C/EBP alpha and DBP in the expression of human CYP3A4 and CYP3A7. J. Hepatol. 1997: 26 Suppl 2, 54-62.
Porter, T. D., Coon, M. J. Cytochrome P-450. Multiplicity of isoforms, substrates, and catalytic and regulatory mechanisms. J. Biol. Chem. 1991: 266, 13469-13472.
Rebbeck, T. R., Jaffe, J. M., Walker, A. H., Wein, A. J., Malkowicz, S. B. Modification of clinical presentation of prostate tumors by a novel genetic variant in CYP3A4. Natl. Cancer Inst. 1998: 90, 1225-1229.
Roh, H. K., Dahl, M. L., Johansson, I., Ingelman-Sundberg, M., Cha, Y. N., Bertilsson, L. Debrisoquine and S-mephenytoin hydroxylation phenotypes and genotypes in a Korean population. Pharmacogenetics 1996: 6, 441-7
Schuetz, J. D., Molowa, D. T., Guzelian, P. S. Characterization of a cDNA encoding a new member of the glucocorticoid-responsive cytochromes P450 in human liver. Arch. Biochem. Biophys. 1989: 274, 355-365.
Schuetz, E. G., Schuetz, J. D., Grogan, W. M., Naray-Fejes-Toth, A., Fejes-Toth, G., Raucy, J., Guzelian, P., Gionela, K., Watlington, C. O. Expression of cytochrome P450 3A in amphibian, rat, and human kidney. Arch. Biochem. Biophys. 1992: 294, 206-214.
Shimada, T., Martin, M. V., Pruess-Schwartz, D., Marnett, L. J., Guengerich, F. P. Roles of individual human cytochrome P-450 enzymes in the bioactivation of benzo(a)pyrene, 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene, and other dihydrodiol derivatives of polycyclic aromatic hydrocarbons. Cancer Res. 1989: 49, 6304-6312.
Shimada, T., Yamazaki, H., Mimura, M., Inui, Y., Guengerich, F. P. Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J. Pharmacol. Exp. Ther. 1994: 270, 414-423.
Sladek, F. M., Zhong, W. M., Lai, E., Darnell, J. E., Jr. Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily. Genes Dev. 1990: 4, 2353-65.
Spurr, N. K., Gough, A. C., Stevenson, K., Wolf, C. R. The human cytochrome P450 CYP3 locus: assignment to chromosome 7q22-qter. Hum. Genet. 1989: 81, 171-174.
Sturm, R. A., Das, G., Herr, W. The ubiquitous octamer-binding protein Oct-1 contains a POU domain with a homeo box subdomain. Genes Dev. 1988: 2, 1582-99.
Szklarz, G. D., Halpert, J. R. Molecular modeling of cytochrome P450 3A4. Comput. Aided. Mol. Des. 1997: 11, 265-72.
Tateishi, T., Krivoruk, Y., Wood, A. J. J., Guengerich, F. P., and Wood, M., 1994, Identification of human liver P450 3A4 as the enzyme responsible for sulfentanil N-dealkylation, in: Abstracts, 12th Int. Congr. Pharmacol. (July 24-29, Montreal).
Tran, J. Q., Kovacs, S. J., McIntosh, T. S., Davis, H. M., Martin, D. E. Morning spot and 24-hour urinary 6 beta-hydroxycortisol to cortisol ratios: intraindividual variability and correlation under basal conditions and conditions of CYP3A4 induction. Clin. Pharmacol. 1999: 39, 487-94.
Vogel, F. & A. G. Motulsky: Human genetics, problems and approaches. Springer-Verlag, Berlin, 1982.
Wang, H., Dick, R., Yin, H., Licad-Coles, E., Kroetz, D. L., Szklarz, G., Harlow, G., Halpert, J. R., Correia, M. A. Structure-function relationships of human livercytochromes P450 3A: aflatoxin B1 metabolism as a probe. Biochemistry 1998 : 37, 12536-45.
Wang, P. P., Beaune, P., Kaminsky, L. S., Dannan, G. A., Kadlubar, F. F., Larrey, D., Guengerich, F. P. Purification and characterization of six cytochrome P-450 isozymes from human liver microsomes. Biochemistry 1983: 22, 5375-5383.
Wang, S. L., Huang, J. D., Lai, M. D., Liu, B. H., Lai, M. L. Molecular basis of genetic variation in debrisoquin hydroxylation in Chinese subjects: polymorphism in RFLP and DNA sequence of CYP2D6. Clin. Pharmacol. Ther. 1993: 53, 410-8.
Watkins, P. B., Wrighton, S. A., Maurel, P., Schuetz, E. G., Mendez-Picon, G., Parker, G. A., Guzelian, P. S. Identification of an inducible form of cytochrome P-450 in human liver. Proc. Natl. Acad. Sci. U S A 1985: 82, 6310-6314.
Watkins, P. B., Wrighton, S. A., Schuetz, E. G., Molowa, D. T., Guzelian, P. S. Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man. Clin. Invest. 1987: 80, 1029-1036.
Watkins, P. B., Turgeon, D. K., Saenger, P., Lown, K. S., Kolars, J. C., Hamilton, T., Fishman, K., Guzelian, P. S., Voorhees, J. J. Comparison of urinary 6-beta-cortisol and the erythromycin breath test as measures of hepatic P450IIIA (CYP3A) activity. Clin. Pharmacol. Ther. 1992: 52, 265-273.
Wrighton, S. A., Stevens, J. C. The human hepatic cytochromes P450 involved in drug metabolism. Crit. Rev. Toxicol. 1992: 22, 1-21.
Wrighton, S. A., VandenBranden, M., Ring, B. J. The human drug metabolizing cytochromes P450. J. Pharmacokinet. Biopharm. 1996: 24, 461-73.
Yanagida, A., Sogawa, K., Yasumoto, K. I., Fujii-Kuriyama, Y. A novel cis-acting DNA element required for a high level of inducible expression of the rat P-450c gene. Mol. Cell. Biol. 1990: 10, 1470-5.
Zhang, Q. Y., Dunbar, D., Ostrowska, A., Zeisloft, S., Yang, J., Kaminsky, L. S. Characterization of human small intestinal cytochromes P-450. Drug Metab. Dispos. 1999: 27, 804-9
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