Biomolecular Free Radical Toxicity Causes and

Biomolecular Free Radical Toxicity: Causes and Prevention provides a comprehensive overview of biomolecular injury. By discussing recent research and providing interpretations of the available data, this unique and timely book explores the causes of biomolecular injury and the possible routes to its prevention. Split into three sections, the book covers: * macromolecular mechanisms of injury and the role of antioxidants; * gene expression and cell mediated mechanisms of toxicity expression; and, * human and environmental health effects. Written by experts in the field, Biomolecular Free Radical Toxicity: Causes and Prevention will be invaluable to researchers specialising in food and nutrition-based toxicology, biomolecular sciences, biochemistry, genetics, environmental biomonitoring, drug metabolism and carcinogenesis.

Helen Wiseman is Lecturer in Nutritional Sciences in the Diabetes and Nutritional Sciences Division at King's College London.

Peter Goldfarb is professor of molecular biology at the School of Biosciences and Medicine, University of Surrey. His research interests include Molecular Toxicology and Pharmacogenetics.

Tim Ridgway is the author of Biomolecular Free Radical Toxicity: Causes and Prevention, published by Wiley.

Alan Wiseman is the author of Biomolecular Free Radical Toxicity: Causes and Prevention, published by Wiley.

Preface

ix

MACROMOLECULAR MECHANISMS OF INJURY AND THE ROLE OF ANTIOXIDANTS

1

(100)

Membrane Lipid and Lipoprotein Injury: Prevention by Antioxidants

3

(44)

Helen Wiseman

Tim Ridgway

Membrane structural and functional features

3

(1)

Oxidative biomolecular injury to membrane lipids

4

(2)

Membrane fatty acids in oxidative biomolecular injury

6

(1)

Prevention of oxidative biomolecular injury by antioxidants in the diet

7

(15)

Dietary modulation of membrane fluidity and of enzyme and receptor activity

22

(2)

Dietary modulation of membranes in disease treatment and prevention?

24

(5)

Lipoprotein particle injury in atherogenesis

29

(6)

Future prospects for antioxidant protection against membrane lipid and lipoprotein injury and for dietary modulation of membrane function in disease prevention

35

(1)

References

36

(11)

DNA Injury: Prevention by Antioxidants

47

(26)

Richard J. Hambly

Oxidative DNA damage

47

(3)

Endogenous cellular antioxidant defences

50

(1)

Oxidative DNA damage and cancer

51

(2)

Dietary antioxidants

53

(2)

Specific antioxidants

55

(3)

Vitamins

58

(5)

References

63

(10)

Protein Injury: Prevention by Antioxidants

73

(28)

Barbara R. Evans

Jonathan Woodward

Oxidative damage to proteins: causes and mechanism

73

(7)

Antioxidants and their application

80

(8)

Two case studies of effects of oxidants

88

(4)

References

92

(9)

GENE EXPRESSION AND CELL MEDIATED MECHANISMS OF TOXICITY EXPRESSION

101

(68)

Xenobiotic Metabolism and Bioactivation by Cytochromes P-450

103

(42)

Costas Ioannides

Metabolism of xenobiotics

104

(1)

Bioactivation of xenobiotics

104

(7)

Chemical carcinogenesis

111

(2)

Cytochromes P-450

113

(3)

Induction and inhibition of cytochromes P-450

116

(3)

Genetic polymorphism in cytochrome P-450 expression

119

(1)

Cytochrome P-450-dependent metabolism of drugs and bioactivation of chemical carcinogens

119

(12)

Cytochrome P-450 induction and chemical carcinogenesis: the Ah receptor

131

(3)

Conclusions

134

(1)

References

135

(10)

Apoptosis Triggered by Free Radicals: Role in Human Diseases

145

(24)

George E.N. Kass

Sek C. Chow

Sten Orrenius

Introduction

145

(1)

Cell death in tissues: apoptosis and programmed cell death

146

(2)

Apoptosis: morphological and biochemical considerations

148

(2)

Free radicals and apoptosis

150

(2)

Free radicals and cell death: apoptosis versus necrosis

152

(1)

Mechanisms of free radical-induced apoptosis

153

(3)

Mitochondria as molecular convergence point for free radical-induced cell death: apoptosis versus necrosis

156

(2)

Caspases as targets for free radicals in necrosis

158

(1)

Conclusions and perspectives

159

(1)

References

160

(9)

HUMAN AND ENVIRONMENTAL HEALTH EFFECTS

169

(64)

Dietary Phytoestrogens, Oestrogens and Tamoxifen: Mechanisms of Action in Modulation of Breast Cancer Risk and Prevention of Heart Disease

171

(38)

Helen Wiseman

Dietary phytoestrogens, oestrogens and tamoxifen: role in modulation of breast cancer risk and in heart disease prevention

171

(1)

Oestrogens and risk of breast cancer

172

(4)

Oestrogens in cardioprotection

176

(1)

The anticancer drug tamoxifen

177

(2)

Tamoxifen metabolism in humans

179

(1)

Tamoxifen as a protective agent against heart disease

180

(5)

Dietary phytoestrogens

185

(1)

Dietary sources, metabolism and bioactivity of isoflavone and lignan phytoestrogens

185

(5)

Health protection by phytoestrogens

190

(5)

Protection by phytoestrogens against cardiovascular disease and osteoporosis

195

(2)

Phytoestrogens: the dangers versus future dietary benefits and use in nutraceutical supplements

197

(2)

References

199

(10)

Strategies for the Removal of Ecotoxicants: Environmental Oestrogens and Oestrogen-Mimics

209

(24)

Tim Ridgway

Helen Wiseman

Oestrogen mimicry in the environment

209

(5)

Development of replacement materials for xenoestrogen avoidance

214

(1)

Activated-carbon filtration of water in the removal of environmental oestrogens and oestrogen-mimics

215

(1)

Use of charged suspended-particles to remove environmental oestrogens and oestrogen-mimics

215

(1)

Chemical catalysis for the removal of environmental oestrogens and oestrogen-mimics

216

(1)

Use of enzymic catalysis in the removal of environmental oestrogens and oestrogen-mimics

217

(5)

Microbial bioremediation of environmental oestrogens and oestrogen-mimics

222

(1)

The use of plants for bioremediation of environmental oestrogens and oestrogen-mimics

223

(1)

A healthy biosphere: progress towards `Techno-Gaia'

224

(1)

Biomonitoring of environmental oestrogens and oestrogen-mimics: leading to ecorestoration?

225

(1)

Prediction of oestrogen-mimicry by biomolecular modelling techniques

225

(2)

Conclusions on ecorestoration after biomonitoring of environmental oestrogens and oestrogen-mimics

227

(6)

Index

233

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Biomolecular Free Radical Toxicity Causes and Prevention

Summary

Author Biography

Table of Contents

Supplemental Materials