Modulations of carcinogenesis in the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

• Other Authors: Leung, Yuet Kin.
• Format: Others
• Language: English; Chinese
• Published: 1998
• Subjects: Nitrosamines > metabolism; Carcinogens > metabolism
• Online Access: http://library.cuhk.edu.hk/record=b5889595; http://repository.lib.cuhk.edu.hk/en/item/cuhk-322232

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