Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 200-205).

Yang Lei. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 141-148). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract --- p.ii / Abstract (Chinese Version) --- p.iv / Table of Contents --- p.vi / List of Abbreviations --- p.xii / List of Figures --- p.xiii / List of Tables --- p.xviii / Chapter Chapter 1 --- Literature review --- p.1 / Chapter 1.1 --- Carbon tetrachloride (CC14) --- p.1 / Chapter 1.2 --- Major uses of CC14 --- p.1 / Chapter 1.3 --- Potential human exposure pathways to CC14 --- p.2 / Chapter 1.4 --- Toxicity of CC14 --- p.3 / Chapter 1.5 --- Mechanism of CCl4-induced hepatotoxicity --- p.5 / Chapter 1.6 --- Role of CYP2E1 involved in CCl4-induced hepatotoxicity --- p.7 / Chapter 1.7 --- Definite proof of the involvement of CYP2E1 in CCl4-induced hepatotoxicity by CYP2El-null mouse in vivo model --- p.10 / Chapter 1.8 --- Identification of CYP2E1 -dependent genes involved in CCl4-induced hepatotoxicity by fluorescent differential display (FDD) --- p.11 / Chapter 1.9 --- Objectives of the study --- p.14 / Chapter Chapter 2 --- Materials and methods --- p.16 / Chapter 2.1 --- Animals and treatments --- p.16 / Chapter 2.1.1 --- Materials --- p.16 / Chapter 2.1.2 --- Methods --- p.16 / Chapter 2.2 --- Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) analyses --- p.17 / Chapter 2.2.1 --- Materials --- p.17 / Chapter 2.2.2 --- Methods --- p.17 / Chapter 2.2.2.1 --- Serum preparation --- p.17 / Chapter 2.2.2.2 --- Activity determination --- p.18 / Chapter 2.3 --- Tail-genotyping by PCR --- p.18 / Chapter 2.3.1 --- Materials --- p.18 / Chapter 2.3.2 --- Methods --- p.20 / Chapter 2.3.2.1 --- Preparation of genomic DNA from mouse tail --- p.20 / Chapter 2.3.2.2 --- PCR reaction --- p.20 / Chapter 2.4 --- Total RNA isolation --- p.21 / Chapter 2.4.1 --- Materials --- p.21 / Chapter 2.4.2 --- Methods --- p.21 / Chapter 2.5 --- DNase I treatment --- p.23 / Chapter 2.5.1 --- Materials --- p.23 / Chapter 2.5.2 --- Methods --- p.23 / Chapter 2.6 --- Reverse transcnption of mRNA and amplification by fluorescent PCR amplification --- p.26 / Chapter 2.6.1 --- Materials --- p.27 / Chapter 2.6.2 --- Methods --- p.27 / Chapter 2.7 --- Fluorescent differential display (FDD) --- p.28 / Chapter 2.7.1 --- Materials --- p.28 / Chapter 2.7.2 --- Methods --- p.28 / Chapter 2.8 --- Excision of differentially expressed cDNA fragments --- p.29 / Chapter 2.8.1 --- Materials --- p.29 / Chapter 2.8.2 --- Methods --- p.29 / Chapter 2.9 --- Reamplification of differentially expressed cDNA fragments --- p.34 / Chapter 2.9.1 --- Materials --- p.34 / Chapter 2.9.2 --- Methods --- p.34 / Chapter 2.10 --- Subcloning of reamplified cDNA fragments --- p.36 / Chapter 2.10.1 --- Materials --- p.36 / Chapter 2.10.2 --- Methods --- p.37 / Chapter 2.11 --- Purification of plasmid DNA from recombinant clones --- p.39 / Chapter 2.11.1 --- Materials --- p.39 / Chapter 2.11.2 --- Methods --- p.39 / Chapter 2.12 --- DNA sequencing of differentially expressed cDNA fragments --- p.40 / Chapter 2.12.1 --- Materials --- p.40 / Chapter 2.12.2 --- Methods --- p.40 / Chapter 2.12.3 --- BLAST search against the GenBank DNA databases --- p.41 / Chapter 2.13 --- Northern blot analysis of differentially expressed cDNA fragments --- p.41 / Chapter 2.13.1 --- Formaldehyde gel electrophoresis of total RNA --- p.41 / Chapter 2.13.1.1 --- Materials --- p.42 / Chapter 2.13.1.2 --- Methods --- p.42 / Chapter 2.13.2 --- Preparation of cDNA probes for hybridization --- p.42 / Chapter 2.13.2.1 --- EcoRI digestion of cDNA inserts from plasmid DNA --- p.42 / Chapter 2.13.2.1.1 --- Materials --- p.42 / Chapter 2.13.2.1.2 --- Methods --- p.43 / Chapter 2.13.2.2 --- Purification of DNA from agarose gel --- p.43 / Chapter 2.13.2.2.1 --- Materials --- p.43 / Chapter 2.13.2.2.2 --- Methods --- p.43 / Chapter 2.13.2.3 --- DIG labeling of cDNA --- p.44 / Chapter 2.13.2.3.1 --- Materials --- p.44 / Chapter 2.13.2.3.2 --- Methods --- p.44 / Chapter 2.13.3 --- Hybridization --- p.45 / Chapter 2.13.3.1 --- Materials --- p.45 / Chapter 2.13.3.2 --- Methods --- p.45 / Chapter Chapter 3 --- Results --- p.47 / Chapter 3.1 --- Liver morphology --- p.47 / Chapter 3.2 --- Serum ALT and AST activities --- p.47 / Chapter 3.3 --- Tail-genotyping by PCR --- p.51 / Chapter 3.4 --- DNase I treatment --- p.51 / Chapter 3.5 --- FDD RT-PCR and excision of differentially expressed cDNA fragments --- p.51 / Chapter 3.6 --- Reamplification of excised cDNA fragments --- p.61 / Chapter 3.7 --- Subcloning of reamplified cDNA fragments --- p.61 / Chapter 3.8 --- DNA sequencing of subcloned cDNA fragments --- p.69 / Chapter 3.9 --- Confirmation of differentially expressed patterns by Northern blot analysis --- p.106 / Chapter 3.10 --- Temporal expression of differentially expressed genes --- p.113 / Chapter 3.11 --- Tissue distribution of differentially expressed genes --- p.117 / Chapter Chapter 4 --- Discussion --- p.125 / Chapter 4.1 --- Liver morphology and serum ALT and AST activities --- p.126 / Chapter 4.2 --- Identification of CYP2E1 -dependent genes involved in CCl4-induced hepatotoxicity --- p.127 / Chapter 4.3 --- Functional roles of the identified differentially expressed genes --- p.129 / Chapter 4.3.1 --- Fragment B4 --- p.129 / Chapter 4.3.2 --- Fragment C12 --- p.130 / Chapter 4.3.3 --- Fragment B13 --- p.131 / Chapter 4.3.4 --- Fragment A5 --- p.132 / Chapter 4.4 --- Temporal expression of differentially expressed genes --- p.133 / Chapter 4.4.1 --- Fragment B4 --- p.133 / Chapter 4.4.2 --- Fragment C12 --- p.134 / Chapter 4.4.3 --- Fragment B13 --- p.134 / Chapter 4.4.4 --- Fragment A5 --- p.135 / Chapter 4.5 --- Tissue distribution of differentially expressed genes --- p.136 / Chapter 4.5.1 --- Fragment B4 --- p.136 / Chapter 4.5.2 --- Fragment C12 --- p.136 / Chapter 4.5.3 --- Fragment B13 --- p.137 / Chapter 4.5.4 --- Fragment A5 --- p.137 / Chapter 4.5.5 --- Roles of the identified genes involved in CCl4-induced hepatotoxicity --- p.138 / Chapter 4.6 --- Normalization of Northern blot analysis --- p.13 8 / Chapter 4.7 --- Limitations of FDD technique to identify differentially expressed genes --- p.138 / Chapter 4.8 --- Future studies --- p.139 / Chapter 4.8.1 --- Investigation of the differential expression patterns of the identified genes in acetaminophen-induced liver injury --- p.139 / Chapter 4.8.2 --- Dot blot analysis --- p.140 / Chapter 4.8.3 --- DNA microarray --- p.140 / References --- p.141

by Wong Wing-yee, Felice. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 144-166). / Abstract also in Chinese. / Acknowledgements --- p.i / List of Abbreviations --- p.ii / Abstract --- p.iv / Abstract (Chinese Version) --- p.vi / Table of Contents --- p.viii / List of Tables --- p.xii / List of Figures --- p.xiv / List of Appendices --- p.xvi / Chapter Chapter I --- Literature Review / Chapter 1. --- Introduction --- p.1 / Chapter 2. --- Background of Cytochrome P450 --- p.3 / Chapter 2.1 --- Discovery --- p.3 / Chapter 2.2 --- Tissue Distribution --- p.3 / Chapter 2.3 --- Structure and Functions --- p.7 / Chapter 2.4 --- Nomenclature of the P450 Superfamily --- p.10 / Chapter 3. --- Cytochrome P450 2E1 (CYP2E1) --- p.11 / Chapter 3.1 --- Discovery --- p.11 / Chapter 3.2 --- Tissue Distribution --- p.12 / Chapter 3.3 --- Substrates and Inducers --- p.13 / Chapter 3.4 --- Toxicological Role of CYP2E1 --- p.15 / Chapter 4. --- CYP2E1-knockout Mouse Model --- p.17 / Chapter Chapter II --- Carbon Tetrachloride (CC14) Study / Chapter 1. --- Introduction --- p.19 / Chapter 1.1 --- General Properties and Usage of CC14 --- p.19 / Chapter 1.2 --- Toxicological Aspects of CC14 --- p.19 / Chapter 1.3 --- Mechanism of CCl4-induced Hepatotoxicity --- p.20 / Chapter 1.4 --- Role of CYP2E1 in CCl4-induced Hepatotoxicity --- p.23 / Chapter 1.5 --- Objectives of the Study --- p.27 / Chapter 2. --- Materials and Methods --- p.29 / Chapter 2.1 --- Chemicals and Materials --- p.29 / Chapter 2.2 --- Animals --- p.29 / Chapter 2.3 --- Acute CC14 Treatment --- p.29 / Chapter 2.4 --- Preparation of Microsomal Fractions --- p.30 / Chapter 2.5 --- Determination of Microsomal Protein Concentration --- p.31 / Chapter 2.6 --- Determination of Serum Aminotransferase Activities --- p.31 / Chapter 2.7 --- Liver Histology --- p.32 / Chapter 2.8 --- Hepatic Microsomal CYP2E1 Activity -p-nitrophenol Assay --- p.34 / Chapter 2.9 --- SDS-PAGE and Western Blot Analysis --- p.35 / Chapter 2.10 --- Detection of Lipid Peroxidation in vitro and in vivo --- p.35 / Chapter 2.10.1 --- In vitro Lipid Peroxidation - 2-Thiobarbituric Acid (TBA) assay --- p.35 / Chapter 2.10.2 --- In vivo Lipid Peroxidation - Microsomal Conjugated Dienes Detection --- p.36 / Chapter 2.11 --- Hepatic Lipid Fatty Acid Composition Analysis --- p.39 / Chapter 2.11.1 --- Lipid Extraction --- p.39 / Chapter 2.11.2 --- Thin Layer Chromatography --- p.39 / Chapter 2.11.3 --- Methylation --- p.40 / Chapter 2.11.4 --- Gas Chromatography --- p.40 / Chapter 2.12 --- Statistical Analysis --- p.41 / Chapter 3. --- Results --- p.42 / Chapter 3.1 --- "Mortality, Liver Weight and Liver Color" --- p.42 / Chapter 3.2 --- Hepatotoxicity --- p.42 / Chapter 3.2.1 --- Serum ALT and AST activities --- p.42 / Chapter 3.2.2 --- Liver Histology --- p.45 / Chapter 3.3 --- CYP2E1-catalysed PNP Activities and CYP2E1 Protein Levels --- p.49 / Chapter 3.3.1 --- CYP2El-catalyzed PNP Activities --- p.49 / Chapter 3.3.2 --- CYP2E1 Protein Levels --- p.52 / Chapter 3.4 --- Lipid Peroxidation --- p.52 / Chapter 3.4.1 --- In vitro Lipid Peroxidation --- p.52 / Chapter 3.4.2 --- In vivo Lipid Peroxidation --- p.54 / Chapter 3.5 --- Hepatic Lipid Fatty Acid Composition --- p.56 / Chapter 3.5.1 --- Fatty Acid Composition in Hepatic Phospholipid --- p.56 / Chapter 3.5.2 --- Fatty Acid Composition in Hepatic Microsomal Phospholipid --- p.59 / Chapter 3.5.3 --- Fatty Acid Composition in Hepatic Triglyceride --- p.61 / Chapter 4. --- Discussion --- p.63 / Chapter 4.1 --- CYP2E1 is Required in CCl4-mediated Hepatotoxicity --- p.63 / Chapter 4.2 --- CYP2E1 is Degraded following CC14 Exposure --- p.65 / Chapter 4.3 --- CYP2E1 is Required in CCl4-induced Lipid Peroxidation --- p.67 / Chapter 4.4 --- CYP2E1 is Required in CCl4-induced Hepatic Phospholipid Depletion --- p.70 / Chapter 4.5 --- CYP2E1 is Required in CCl4-induced Hepatic Triglyceride Accumulation --- p.72 / Chapter 5. --- Conclusion --- p.76 / Chapter Chapter III --- Chronic Ethanol Consumption Study / Chapter 1. --- Introduction --- p.77 / Chapter 1.1 --- Multiple Metabolic Pathways for Ethanol Metabolism --- p.77 / Chapter 1.2 --- Metabolism of Ethanol by the Microsomal Ethanol Oxidizing System --- p.79 / Chapter 1.3 --- Role of CYP2E1 in Ethanol Metabolism --- p.82 / Chapter 1.4 --- Role of CYP2E1 in Alcoholic Liver Disease and Associated Oxidative Stress --- p.84 / Chapter 1.5 --- Objectives of the Study --- p.89 / Chapter 2. --- Materials and Methods --- p.90 / Chapter 2.1 --- Chemicals and Materials --- p.90 / Chapter 2.2 --- Animals --- p.90 / Chapter 2.3 --- Chronic Ethanol Treatment --- p.90 / Chapter 2.3.1 --- Ethanol Diet Composition --- p.90 / Chapter 2.3.2 --- Ethanol Feeding --- p.90 / Chapter 2.4 --- Monitoring of Blood Ethanol Levels --- p.96 / Chapter 2.5 --- Preparation of Microsomal Fractions --- p.96 / Chapter 2.6 --- Determination of Microsomal Protein Concentration --- p.97 / Chapter 2.7 --- Determination of Serum Aminotransferase Activities --- p.98 / Chapter 2.8 --- Liver Histology --- p.98 / Chapter 2.9 --- SDS-PAGE and Western Blot Analysis --- p.99 / Chapter 2.10 --- Hepatic Fatty Acid Composition Analysis --- p.100 / Chapter 2.10.1 --- Lipid Extraction --- p.100 / Chapter 2.10.2 --- Thin Layer Chromatography --- p.101 / Chapter 2.10.3 --- Methylation --- p.101 / Chapter 2.10.4 --- Gas Chromatography --- p.102 / Chapter 2.11 --- Statistical Analysis --- p.103 / Chapter 3. --- Results --- p.104 / Chapter 3.1 --- Average Food Consumption --- p.104 / Chapter 3.2 --- Average Ethanol Consumption for Ethanol Liquid Diet Feeding Group --- p.104 / Chapter 3.3 --- Body Weight Gain --- p.104 / Chapter 3.4 --- Blood Ethanol Levels --- p.108 / Chapter 3.5 --- "Mortality, Liver Weight and Liver Color" --- p.108 / Chapter 3.6 --- Serum ALT and AST Activities --- p.110 / Chapter 3.7 --- Liver Histology --- p.114 / Chapter 3.8 --- Western Blot Analysis --- p.119 / Chapter 3.9 --- Hepatic Lipid Fatty Acid Composition --- p.119 / Chapter 3.9.1 --- Fatty Acid Composition in Hepatic Phospholipid --- p.119 / Chapter 3.9.2 --- Fatty Acid Composition in Hepatic Triglyceride --- p.123 / Chapter 4. --- Discussion --- p.126 / Chapter 4.1 --- Nutrients Displacement after Chronic Ethanol Consumption --- p.126 / Chapter 4.2 --- Varied Blood Ethanol Levels after Chronic Ethanol Consumption --- p.127 / Chapter 4.3 --- Increase in CYP2E1 Levels after Chronic Feeding of Ethanolin WT mice --- p.127 / Chapter 4.4 --- Lack of Evidence Indicating the Development of Ethanol- Induced Liver Injury --- p.129 / Chapter 4.4.1 --- No Elevations in Serum ALT and AST Activities --- p.129 / Chapter 4.4.2 --- Normal Liver Histology --- p.130 / Chapter 4.4.3 --- Lack of Triglyceride Accumulation --- p.131 / Chapter 4.4.4 --- Elevations in Hepatic PL --- p.132 / Chapter 4.5 --- Possible Reasons for the Absence of Liver Damage after Chronic Ethanol Consumption in our Mouse Model --- p.134 / Chapter 5. --- Conclusion --- p.137 / Chapter Chapter IV --- Concluding Remarks / Chapter 1. --- A Comparison between Acute CC14 Study and Chronic Ethanol Consumption Study --- p.139 / Chapter 1.1 --- Regulation of CYP2E1 Expression --- p.139 / Chapter 1.2 --- Free Radical Production Involved in CC14- and Chronic Ethanol Consumption-Mediated Liver Injury --- p.140 / Chapter 1.3 --- An Overall Comparison between CC14 study and Chronic Ethanol Consumption Study --- p.140 / Chapter 2. --- Future Studies --- p.142 / Chapter 2.1 --- Acute CC14 Study --- p.142 / Chapter 2.1.1 --- Calcium Homeostasis Studies --- p.142 / Chapter 2.1.2 --- Spin Trapping Studies --- p.142 / Chapter 2.2 --- Chronic Ethanol Study --- p.142 / Chapter 2.2.1 --- "Generation of a Heterozygous ""Ethanol-Sensitive"" Mouse Strain (SV/129/ter x C57BL/6)" --- p.143 / Chapter 3. --- Concluding Remarks --- p.143 / References --- p.144 / Appendix --- p.167

Avasarala Sreedevi. / "December 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 253-272) / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Cheung, Ching Mei. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 151-162). / Abstracts in English and Chinese. / ABSTRACT --- p.I / 論文摘要 --- p.IV / ACKNOWLEDGEMENT --- p.VI / TABLE OF CONTENTS --- p.VII / ABBREVIATIONS --- p.X / Chapter Chapter 1 --- p.1 / GENERAL INTRODUCTION --- p.1 / Chapter 1.1 --- DANSHEN --- p.1 / Chapter 1.1.1 --- LIPID-SOLUBLE COMPOUNDS EXTRACTED FROM DANSHEN --- p.2 / Chapter 1.1.1.1 --- TANSHINONE I --- p.2 / Chapter 1.1.1.2 --- TANSHINONE IIA --- p.3 / Chapter 1.1.1.3 --- CRYPTOTANSHINONE --- p.3 / Chapter 1.1.1.4 --- DIHYDROTANSHINONE --- p.4 / Chapter 1.1.2 --- WATER-SOLUBLE COMPOUNDS EXTRACTED FROM DANSHEN --- p.4 / Chapter 1.1.2.1 --- DANSHENSU --- p.4 / Chapter 1.1.2.2 --- SALVIANOLIC ACID B --- p.5 / Chapter 1.2 --- DRUG-DRUG INTERACTIONS --- p.5 / Chapter 1.2.1 --- PROBLEMS ASSOCIATED WITH HERBAL ADMINISTRATION --- p.5 / Chapter 1.2.2 --- HERB-DRUG INTERACTIONS --- p.7 / Chapter 1.2.2.1 --- ST. JOHŃةS WORT-DRUG INTERACTIONS --- p.8 / Chapter 1.2.2.2 --- WARFARIN-HERB INTERACTIONS --- p.9 / Chapter 1.2.2.3 --- DANSHEN-WARFARIN INTERACTIONS --- p.10 / Chapter 1.2.2.4 --- DANSHEN-DRUG INTERACTIONS --- p.11 / Chapter 1.3 --- CYTOCHROME P450 ENZYMES (CYP) --- p.12 / Chapter 1.3.1 --- CYTOCHROME P4502E1 --- p.13 / Chapter 1.4 --- AIMS OF STUDY --- p.17 / Chapter Chapter 2 --- p.21 / EFFECTS OF DANSHEN AND SOME IF ITS ACTIVE COMPONENTS ON CHLORZOXAZONE METABOLISM IN RAT AND HUMAN LIVER MICROSOMES IN VITRO --- p.21 / Chapter 2.1 --- INTRODUCTION --- p.21 / Chapter 2.2 --- MATERIALS AND METHODS --- p.23 / Chapter 2.2.1 --- CHEMICALS AND REAGENTS --- p.23 / Chapter 2.2.2 --- PREPARATION OF AQUEOUS FRACTION OF DANSHEN --- p.23 / Chapter 2.2.3 --- PREPARATION OF ETHANOLIC FRACTION OF DANSHEN --- p.23 / Chapter 2.2.4 --- ANIMALS --- p.24 / Chapter 2.2.5 --- PREPARATION OF RAT LIVER MICROSOMES --- p.25 / Chapter 2.2.6 --- POOLED HUMAN LIVER MICROSOMES --- p.25 / Chapter 2.2.7 --- PROTEIN ASSAY --- p.25 / Chapter 2.2.8 --- MICROSOMAL INCUBATION --- p.26 / Chapter 2.2.8.1 --- RAT LIVER MICROSOMES --- p.26 / Chapter 2.2.8.2 --- HUMAN LIVER MICROSOMES --- p.26 / Chapter 2.2.9 --- INHIBITION KINETICS STUDIES --- p.27 / Chapter 2.2.9.1 --- RAT LIVER MICROSOMES --- p.27 / Chapter 2.2.9.2 --- HUMAN LIVER MICROSOMES --- p.27 / Chapter 2.2.10 --- HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC) ANALYSIS --- p.28 / Chapter 2.2.11 --- DATA ANALYSIS --- p.28 / Chapter 2.3 --- RESULTS --- p.31 / Chapter 2.3.1 --- EFFECT OF DANSHEN AND TANSHINONES ON RAT CYP2E1 ACTIVITY IN VITRO / Chapter 2.3.1.1 --- SUMMARY --- p.57 / Chapter 2.3.2 --- EFFECT OF DANSHEN AND TANSHINONES ON HUMAN CYP2E1 ACTIVITYIN VITRO --- p.58 / Chapter 2.3.2.1 --- SUMMARY --- p.84 / Chapter 2.4 --- DISCUSSION --- p.85 / Chapter Chapter 3 --- p.93 / EFFECTS OF DANSHEN ON CYTOCHROME P450 PROTEIN EXPRESSION AND METABOLISM OF MODEL CYP2E1 PROBE SUBSTRATE IN THE RAT IN VIVO --- p.93 / Chapter 3.1 --- INTRODUCTION --- p.93 / Chapter 3.2 --- MATERIALS AND METHODS --- p.97 / Chapter 3.2.1 --- CHEMICALS AND REAGENTS --- p.97 / Chapter 3.2.2 --- ANIMALS --- p.97 / Chapter 3.2.3 --- EFFECTS OF DANSHEN TREATMENTS ON PHARMACOKINETICS OF CHLORZOXAZONE IN RATS IN VIVO --- p.98 / Chapter 3.2.3.1 --- "ACUTE, 3-DAY AND 14-DAY TREATMENTS WITH WHOLE DANSHEN EXTRACT" --- p.98 / Chapter 3.2.3.2 --- PLASMA EXTRACTION --- p.99 / Chapter 3.2.3.3 --- HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC) ANALYSIS --- p.99 / Chapter 3.2.4 --- EFFECTS OF 3-DAY AND 14-DAY DANSHEN TREATMENTS ON CYP2E1 PROTEIN EXPRESSION --- p.101 / Chapter 3.2.4.1 --- PREPARATION OF RAT LIVER MICROSOMES FOR WESTERN BLOTTING --- p.101 / Chapter 3.2.4.2 --- PROTEIN ASSAY --- p.101 / Chapter 3.2.4.3 --- WESTERN BLOT --- p.102 / Chapter 3.2.5 --- DATA ANALYSIS --- p.103 / Chapter 3.3 --- RESULTS --- p.105 / Chapter 3.3.1 --- EFFECTS OF WHOLE DANSHEN EXTRACT ON RAT CYP2E1 ACTIVITIES IN VIVO --- p.105 / Chapter 3.3.1.1 --- EFFECTS OF ACUTE TREATMENTS OF WHOLE DANSHEN EXTRACT ON PHARMACOKINETICS OF CHLORZOXAZONE --- p.105 / Chapter 3.3.1.2 --- EFFECTS OF 3-DAY TREATMENTS OF WHOLE DANSHEN EXTRACT ON PHARMACOKINETICS OF CHLORZOXAZONE --- p.106 / Chapter 3.3.1.3 --- EFFECTS OF 14-DAY TREATMENTS OF WHOLE DANSHEN EXTRACT ON PHARMACOKINETICS OF CHLORZOXAZONE --- p.107 / Chapter 3.3.2 --- EFFECTS OF WHOLE DANSHEN EXTRACT ON RAT CYP2E1 EXPRESSION .… --- p.137 / Chapter 3.3.3 --- SUMMARY --- p.140 / Chapter 3.4 --- DISCUSSION --- p.141 / CHAPTER 4 --- p.145 / GENERAL DISCUSSION --- p.145 / REFERENCES --- p.151

Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 117-125).

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Made available in DSpace on 2016-01-26T12:51:47Z (GMT). No. of bitstreams: 1 glauciamariamfernandes_dissert.pdf: 1922219 bytes, checksum: f00f507bdc9bcdc1daa422a7965c5c41 (MD5) Previous issue date: 2013-12-12 / Fundação de Amparo a Pesquisa do Estado de São Paulo / Introduction: The xenobiotics are exogenous substances to the organism, as N-nitrosamines, heterocyclic amines (HAs) and polycyclic aromatic hydrocarbons (PAHs), can which result in DNA adducts formation. Polymorphisms in genes involved in the metabolism of xenobiotics could contribute to this process and modulate the development of cancer. Objectives: To investigate the CYP1A1*2A (rs4646903), CYP1A1*2C (rs1048943), CYP2E1*5B (rs2031920), CYP1E1*6 (rs6413432), Tyr113His EPHX1 (rs1051740) and His139Arg EPHX1 (rs2234922) polymorphisms related to the metabolism of xenobiotics, the risk of sporadic colorectal (SCRC) cancer, the interaction of these polymorphisms with lifestyle (smoking and drinking) and clinical and histopathological parameters and to evaluate the association of SCRC with socio-demographic factors. Methods: A case-control study was conducted in 641 subjects in the Brazilian population (241 patients with colorectal cancer and 400 controls (individuals without a history of cancer). Real-Time PCR and PCR-RFLP was performed for genotyping. Statistical analysis was performed using the chi-square tet and multiple logistic regression binary. Results: The results showed statistically significant differences between the case and control groups for age greater than 50 years (OR=8.21, 95%CI=5.49-12.28, p<0.01) and male gender (OR=0.50, 95%CI=0.32-0.87, p<0.01) The analysis of polymorphisms revealed an association between the alleles polymorphic CYP2E1*5B (OR=2.84, 95%CI=1.78-4.52, p<0.01, additive model) and CYP2E1*6 (OR=2.78, 95%CI=1.91-4.06, p<0.01, additive model) and the SCRC. Tumor size, lymph node involvement and disease primary site were not associated with polymorphisms. Conclusion: The CYP2E1*5B and CYP2E1*6 polymorphisms are involved in the risk of SCRC and individuals with age &#8805; 50 years are more susceptible to this tumor type, of males are less susceptible. / Introducão: Os xenobióticos são substâncias exógenas ao organismo, tais como as N-nitrosaminas, aminas heterocíclicas (HAs) e hidrocarbonetos policíclicos aromáticos (HPAs), que podem formar adutos de DNA. Polimorfismos em genes envolvidos no metabolismo dos xenobióticos podem contribuir com este processo e, consequentemente, modular o desenvolvimento de câncer. Objetivos: Investigar os polimorfismos CYP1A1*2A (rs 4646903), CYP1A1*2C (rs1048943), CYP2E1*5B (rs 2031920), CYP1E1*6 (rs 6413432), EPHX1 Tyr113His (rs1051740) e EPHX1 His139Arg (rs2234922), relacionados com o metabolismo dos xenobióticos, no risco de câncer de colorretal esporádico (CCRE), a interação desses polimorfismos com os hábitos de vida (tabagismo e etilismo) e parâmetros clínico-histopatológicos e avaliar a associação do CCRE com os fatores sócio-demográficos. Os Métodos: Um estudo caso-controle foi realizado em 641 indivíduos da população brasileira (241 pacientes com câncer de coloretal e 400 controles (indivíduos sem histórico de câncer). As técnicas de PCR em Tempo Real e PCR-RFLP foram realizadas para a genotipagem dos polimorfismos. A análise estatística utilizou os testes de Qui-Quadrado e Regressão Logística Múltipla Binária. Resultados: Os resultados mostraram diferenças estatisticamente significantes entre os grupos caso e controle para idade superior a 50 anos (OR=8,21; IC95%=5,49-12,28, p<0,01) e gênero masculino (OR=0,50; IC95%=0,32-0,87, p<0,01). A análise dos polimorfismos revelou associação entre os alelos polimórficos CYP2E1*5B (OR=2,84; IC95%=1,78-4,52; p<0,01, modelo aditivo) e CYP2E1*6 (OR=2,78; IC95%=1,91-4,06, p<0,01, modelo aditivo) e o CCRE. O tamanho do tumor, envolvimento de linfonodos e sítio primário da doença não foram associados com os polimorfismos. Conclusão: Os polimorfismos CYP2E1*5B e CYP2E1*6 estão envolvidos no risco de CCRE e indivíduos com idade superior ou igual a 50 anos são mais suscetíveis a este tipo tumoral, enquanto aqueles do gênero masculino são menos suscetíveis.