by Leung Yuet Kin. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 86-100). / Abstract also in Chinese. / List of Figures --- p.ix / List of Tables --- p.xii / List of Abbreviations --- p.xiii / Chapter Chapter One: --- Introduction / Chapter 1.1 --- Carcinogenicity of the tobacco products --- p.1 / Chapter 1.2 --- Biochemical Pathway involved in NNK metabolism --- p.5 / Chapter 1.2.1 --- Metabolic activation of NNK --- p.6 / Chapter 1.2.2 --- Detoxification of NNK --- p.8 / Chapter 1.3 --- Modulation of NNK carcinogenesis --- p.9 / Chapter 1.4 --- Mediation of NNK oxidation : chemoprevention by isothiocyanates --- p.11 / Chapter 1.5 --- Aim of study --- p.13 / Chapter 1.5.1 --- Experimental approaches --- p.15 / Chapter Chapter Two : --- Modulation of α-carbon hydroxylations in NNK metabolism / Chapter 2.1 --- Background --- p.17 / Chapter 2.2 --- Materials and Methods --- p.17 / Chapter 2.2.1 --- Chemicals --- p.17 / Chapter 2.2.2 --- Methods --- p.18 / Chapter 2.2.2.1 --- Preparation of rat microsomes --- p.18 / Chapter 2.2.2.2 --- Assay of NNK metabolism --- p.18 / Chapter 2.2.2.3 --- Determination of solvent extraction --- p.19 / Chapter 2.2.2.4 --- Determination of detergent effects --- p.19 / Chapter 2.2.2.5 --- HPLC analysis of NNK metabolites --- p.20 / Chapter 2.2.2.6 --- Study of strain differences between SD rats and F344 rats --- p.20 / Chapter 2.3 --- Results --- p.21 / Chapter 2.3.1 --- HPLC analysis of NNK metabolites --- p.21 / Chapter 2.3.2 --- Determination of solvent extraction --- p.22 / Chapter 2.3.3 --- Effects of detergents --- p.25 / Chapter 2.3.4 --- Study of strain differences using F344 rats and SD rats --- p.26 / Chapter 2.4 --- Discussion --- p.27 / Chapter Chapter Three : --- Modulation by potentiation of detoxification process in NNK metabolism / Chapter 3.1 --- Background --- p.30 / Chapter 3.2 --- Materials and Methods --- p.31 / Chapter 3.2.1 --- Chemicals --- p.31 / Chapter 3.2.2 --- Methods --- p.32 / Chapter 3.2.2.1 --- Preparation of rat microsomes --- p.32 / Chapter 3.2.2.2 --- Analysis of NNK metabolism --- p.32 / Chapter 3.2.2.3 --- UDP-glucuronosyltransferase Assay --- p.33 / Chapter 3.2.2.4 --- Cytochrome P450 2E1 Assay --- p.34 / Chapter 3.3 --- Results --- p.34 / Chapter 3.3.1 --- Screening tests of the effects of vitamins and drugs --- p.34 / Chapter 3.3.1.1 --- Male liver microsomes --- p.35 / Chapter 3.3.1.2 --- Female liver microsomes --- p.37 / Chapter 3.3.1.3 --- Male lung microsomes --- p.39 / Chapter 3.3.1.4 --- Female lung microsmes --- p.41 / Chapter 3.3.2 --- Kinetic analysis of vitamin C-palmitate on NNK reduction --- p.43 / Chapter 3.3.3 --- Effects of vitamin C-palmitate on UDP- glucuronosyltransferase --- p.47 / Chapter 3.3.4 --- Effects of vitamin C-palmitate on cytochrome P4502E1 (CYP2E1) --- p.48 / Chapter 3.4 --- Discussion --- p.50 / Chapter Chapter Four: --- Purification of carbonyl reductase from rat liver microsomes / Chapter 4.1 --- Background --- p.58 / Chapter 4.2 --- Materials and Methods --- p.58 / Chapter 4.2.1 --- Chemicals --- p.58 / Chapter 4.2.2 --- Methods --- p.59 / Chapter 4.2.2.1 --- Preparation of male rat liver microsomes --- p.59 / Chapter 4.2.2.2 --- Purification of carbonyl reductase from rat liver microsomes --- p.59 / Chapter A. --- Solubilization of microsomes --- p.59 / Chapter B. --- Chromatographic separation by octyl-Sepharose CL-4B --- p.60 / Chapter C. --- Chromatographic separation by DEAE-cellulose --- p.60 / Chapter 4.2.2.3 --- SDS polyacrylamide gel electrophoresis --- p.61 / Chapter 4.3 --- Results --- p.61 / Chapter 4.4 --- Discussion --- p.63 / Chapter Chapter Five : --- Summary and Discussion / Chapter 5.1 --- Summary --- p.66 / Chapter 5.2 --- Discussion --- p.67 / Chapter 5.2.1 --- Anticarcinogenesis of vitamin C in NNK-induced cancer through smoking --- p.67 / Chapter 5.2.2 --- Future studies on microsomal carbonyl reductase --- p.68 / Chapter 5.2.3 --- Future studies on UDP-glucuronidation of NNAL --- p.72 / Appendix A Effects of atropine on tolbutamide metabolism --- p.74 / Appendix B Recovery of keto acid and keto alcohol from the assay mixture ( without solvent extraction ) --- p.75 / Appendix C Calibration Curve of NNAL --- p.76 / Appendix D Effects of methanol on NNK carbonyl reduction --- p.77 / Appendix E Time course study of NNAL production at various concentrations of vitamin C-palmitate --- p.78 / Appendix F Time course assay of UDP-glucuronosyltransferase at various concentrations of vitamin C-palmitate --- p.80 / Appendix G Calculation of specific activity of UDP-Glucuronosyl transferase --- p.82 / Appendix H Calculation of specific activity of cytochrome P450 2E1 --- p.84 / References --- p.86
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_322232 |
| Date | January 1998 |
| Contributors | Leung, Yuet Kin., Chinese University of Hong Kong Graduate School. Division of Biochemistry. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, bibliography |
| Format | print, xiv, 100 leaves : ill. ; 30 cm. |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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