DNA Damage and Cell Lethality by Photodynamically Produced Oxygen Radicals

BY PAULA ELLEN BURCH

A Thesis Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy

RICE UNIVERSITY

HOUSTON, TEXAS

April 21, 1989

TABLE OF CONTENTS

ABSTRACT ii
ACKNOWLEDGEMENTS iv
LIST OF FIGURES vii
LIST OF TABLES xii
LIST OF ABBREVIATIONS xiii
CHAPTER I. INTRODUCTION AND LITERATURE REVIEW 1
Oxygen Toxicity 1
Defenses Against Oxygen Toxicity 14
The Photodynamic Effect 27
CHAPTER II. REACTIONS OF DYES 57
Introduction 57
Materials and Methods59
Results 61
CHAPTER III. HYDROXYL RADICAL PRODUCTION IN VITRO82
Introduction 82
Materials and Methods 83
Results 86
CHAPTER IV. DNA DAMAGE IN VITRO 116
Introduction 116
Materials and Methods. 117
Results 118
CHAPTER V. DNA DAMAGE IN VIVO AND OTHER IN VIVO EXPERIMENTS 152
Introduction 152
Materials and Methods 158
Results165
CHAPTER VI. CONCLUSIONS. 178
VII. REFERENCES [have been placed at foot of each chapter]185




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