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Chromosomal Alterations

Methods, Results and Importance in Human Health

By: Gunter Obe (Editor), Vijayalaxmi (Editor)

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Hardcover | 3 July 2007

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540 Pages

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23.5 x 16.51 x 2.54

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Cytogenetics is a very important research tool in basic and applied research. The uses of cytogenetics in human-population monitoring, in biological dosimetry in radiation accidents and in astronauts and as a predictive measure of cancer are topics discussed in this book. The book will help the reader to better understand cytogenetics and the intricacies of the methodology. The different methods of fluorescence in situ hybridization are discussed and the results achieved are presented. The book provides a comprehensive review of basic and applied aspects of cytogenetics and therefore will be of interest to all who are interested in chromosomes and their alterations by different types of mutagens, including chemical mutagens and ionizing and nonionizing radiation, with special reference to electromagnetic fields. Both editors have a year long experience in cytogenetic research and have published many papers in peer reviewed journals on different topics of cytogenetics.

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Non-Fiction Medicine Pre-Clinical Medicine & Basic Sciences Medical Genetics Science Biology, Life Sciences Cellular Biology Biochemistry Clinical & Internal Medicine Diseases & Disorders Oncology

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Paperback

Published: 19th January 2012

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Human Chromosomes: Structural and Functional Aspects	p. 1
History of Chromosome Research	p. 2
Composition and Compartmentalization of Human Chromosomes	p. 4
The Human Karyotype and Clinical Cytogenetics	p. 5
Cell Cycle and Chromosome Cycle	p. 9
Shaping the Metaphase Chromosome	p. 10
Cohesion and Condensins	p. 11
DNA Repair	p. 13
Mendelian Disorders Affecting Chromosome Integrity	p. 14
Chromosome Instability Disorders	p. 14
PCC Syndrome	p. 15
Further Syndromes Affecting Structural Maintenance of the Chromosome	p. 16
References	p. 17
DNA Lesions Induced by Ionizing Radiation	p. 21
introduction	p. 21
Energy Deposition by Ionizing Radiation	p. 23
Direct and Indirect Effect	p. 24
Cerenkov Radiation	p. 25
Hole and Electron Transfer Through DNA	p. 25
Formation of Base Radicals	p. 25
Base Damage	p. 27
Single-Strand Breaks	p. 30
Double Lesions	p. 31
DNA-DNA Cross-Links	p. 34
DNA-Protein Cross-Links	p. 34
Clustered Lesions Beyond Double Lesions	p. 34
Oxygen Effect and Chemical Repair	p. 34
DNA Damage by UV-C and Ionizing Radiation - a Comparison	p. 35
References	p. 36
Effects of Ultraviolet Radiation on DNA	p. 39
Introduction	p. 39
Primary Photoproducts in DNA	p. 42
Action Spectra	p. 44
Reversal and Repair of Primary Photoproducts	p. 46
Cytological Effects	p. 47
Chromosomal Aberrations	p. 47
Micronuclei	p. 49
Sister-Chromatid Exchanges	p. 50
Conclusions	p. 51
References	p. 51
Double Strand Break Repair Mechanisms in Mammalian Cells	p. 55
Introduction	p. 55
NHEJ Reaction	p. 56
NHEJ Mechanism and Junction Formation	p. 56
Proteins Involved in NHEJ	p. 58
DSB Repair by HRR	p. 59
HRR Mechanisms	p. 61
Proteins Involved in HRR	p. 61
Impaired DSB Repair and Chromosomal Aberrations	p. 61
Fragile Sites Are Associated with DNA DSBs	p. 62
Conclusions	p. 63
References	p. 63
Backup Pathways of Nonhomologous End Joining May Have a Dominant Role in the Formation of Chromosome Aberrations	p. 67
Introduction	p. 67
Pathways of DSB Repair	p. 69
Homology-Dependent Pathways of DSB Repair	p. 70
Homology-Independent Pathways of DSB Repair	p. 71
DNA-Dependent NHEJ	p. 72
Backup NHEJ	p. 75
Homology-Independent End Joining and Chromosome Aberration Formation	p. 77
DSBs, NHEJ and Theories of Chromosome Aberration Formation	p. 78
References	p. 83
Targeted and Non-Targeted Induction of Chromosomal Rearrangements After Exposure to Ionizing Radiation	p. 87
Introduction	p. 87
Radiation-Induced Chromosomal Instability	p. 88
The Death-Inducing Effect	p. 90
Chromosomal Instability Induced by DIE Medium from Unstable Clones	p. 93
A Role for Non-Targeted Bystander Effects in Radiation-Induced Chromosomal Instability	p. 93
Implications of Non-Targeted Effects for Cytogenetic Biodosimetry	p. 94
Conclusions	p. 95
References	p. 95
DNA Methylation Damage: Formation, Repair and Biological Consequences	p. 99
Methylating Agents as Environmental Carcinogens	p. 99
Anticancer Drugs	p. 100
DNA Lesions, Sites of Attack	p. 101
Repair of DNA Methylation Damage	p. 104
Reversal Repair	p. 104
Single-Step Repair by MGMT	p. 104
DNA Damage Reversal by AlkB Homologues	p. 104
Mismatch Repair	p. 105
Base Excision Repair	p. 106
Mechanism of Mutagenicity and Carcinogenicity	p. 108
Mechanism of Cytotoxicity of Methylating Agents by Apoptosis	p. 109
Mechanism of Formation of SCEs and Aberrations	p. 111
Critical lesions	p. 111
Involvement of MMR	p. 112
Conversion Rates	p. 113
Critical Role of Inhibition of Replication Fork Movement	p. 114
References	p. 115
Adducts, Sister-Chromatid Exchanges and Mutations Following Benzo[a]pyrene Exposure: a Review of Quantitative Data Followed by Some Considerations Regarding Risk	p. 123
Introduction	p. 123
Methodological Approach	p. 124
Results	p. 125
Adducts	p. 125
BaP Exposure in Vitro: Dose-Effect Relationship for Adduct Formation	p. 125
Adducts in Vivo	p. 127
BPDE Adducts Following BPDE Exposure	p. 128
Human BaP Adducts in Vivo: Comparison with Endogenous Adducts	p. 128
Sister-Chromatid Exchanges	p. 130
Mutations	p. 131
Mutations in Vivo in Animals Following BaP Exposure	p. 131
Mutations in Vitro Following BaP Exposure	p. 132
Discussion	p. 132
Cancer Risk Associated with a Certain Level of BaP Adducts	p. 134
Supralinear Dose-Effect Relationship	p. 137
References	p. 138
Analysis of DNA Double-Strand Breaks by Means of -H2AX Foci	p. 145
Introduction	p. 145
Histone H2AX	p. 146
Histone H2AX Is Phosphorylated in Response to Induction of DNA Double-Strand Breaks	p. 146
-H2AX Is Present in the Nuclear Foci	p. 147
The Phosphatidylinositol 3-Kinase-Like Protein Kinases Are the Main Enzymes that Phosphorylate Histone H2AX	p. 147
Megabase Chromatin Domains Alter Conformation After H2AX Phosphorylation	p. 149
Repair and Checkpoint Factors Are Recruited into -H2AX Foci	p. 149
Early DSB Rejoining Can Proceed Without Foci Formation	p. 150
Foci May Be Present Long After DSB Are Rejoined	p. 150
Practical Aspects of -H2AX Estimation	p. 151
Foci Size and Phosphorylation Heterogeneity	p. 152
-H2AX Foci Frequency As a Measure of Radiosensitivity	p. 154
-H2AX Foci Size and Frequency Depending on Radiation Quality	p. 157
Concluding Remarks	p. 157
References	p. 158
Comet Assay	p. 161
Introduction	p. 161
Method	p. 162
Basic Aspects	p. 162
Scoring of Comets	p. 163
Methods Aimed at the Detection of Specific Types of DNA Damage	p. 163
Problem of Standardization of Methods	p. 165
Detection Limits	p. 165
Factors That Might Affect the outcome of Comet Analyses	p. 166
Age	p. 166
Gender	p. 166
Smoking	p. 167
Alcohol	p. 167
Season	p. 167
Physical Exercise	p. 167
Environmental Exposures	p. 167
Advantages/Disadvantages	p. 168
Applications	p. 169
Individual Radiosensitivity	p. 170
Hypoxic Cells	p. 170
Genotoxicity of Chemicals and Identification of Carcinogenic Substances	p. 170
Predictor of Cancer Risk	p. 170
Biomonitoring	p. 171
Assessment of Exposure to Ionizing Radiation in Vivo	p. 171
UV Damage	p. 172
Final Remark	p. 172
References	p. 172
Origin of Chromosome Aberrations: Mechanisms	p. 177
Introduction	p. 177
Primary DNA Damage	p. 179
Models of Chromosome Aberration Formation	p. 181
The Breakage-First Model	p. 181
The Molecular Misrecombination Model	p. 185
The Transcription-Based Model	p. 186
Models of Chromatid Aberration Formation	p. 187
Formation and Disappearance of Chromatid Breaks	p. 187
Models of Chromatid Breakage	p. 189
The Revell `Exchange' Model	p. 190
The Misrecombination Model	p. 192
The Signal Model	p. 193
Conclusions	p. 194
References	p. 194
Chromatin Structure and the Formation of Chromosomal Alterations	p. 201
Introduction	p. 201
Modelling of Virtual Radiation Events	p. 202
Modelling Results	p. 203
Conclusions	p. 207
References	p. 208
Role of Chromatin Structure and Activity in the Induction of Chromosomal Aberrations	p. 211
Introduction	p. 211
Methodological Aspects	p. 213
Localization of Radiation-Induced Breakpoints on CHO G-banded Chromosomes	p. 213
Immunolabelling of CHO Acetylated H4 Histones and Densitometric Analysis	p. 213
Etoposide and MMS Treatments on CHO Cells: Breakpoint Mapping on the CHO X Chromosome	p. 214
Radiation Exposure of Human Cell Lines with Different Numbers of X Chromosomes	p. 214
Fluorescence in Situ Hybridization	p. 214
BrdUrd Incorporation and Immunolabelling	p. 215
In Situ Nick Translation	p. 215
Distribution of Chromosome Breakpoints in CHO Cells	p. 215
Mapping of Radiation-Induced Breakpoints	p. 215
Histone Acetylation Pattern and Clustering of Breakpoints	p. 216
Distribution of Breakpoints Induced by Etoposide and MMS in the X Chromosome of CHO Cells	p. 217
Chromosome Damage in Human Cell Lines with Multiple X Chromosomes	p. 219
Replication Timing of Active and Inactive Human X Chromosomes	p. 219
Nuclease Sensitivity of Human Metaphase Chromosomes	p. 219
Chromosomal Aberrations Induced by -rays in Human X Chromosomes	p. 221
Conclusion	p. 221
References	p. 221
A Biomedical Perspective of Telomere Structure and Function	p. 225
Introduction	p. 225
The Complex Molecular Structure of the Terminal Chromosome Region	p. 226
Telomeric DNA and Telomerase: Cell Senescence and Cancer	p. 226
Telomeric Chromatin	p. 227
Cryptic Subtelomeric Aberrations: Their Importance in Human Health	p. 228
Light Microscope Methods for the Study of Telomere Structure	p. 229
T-banding	p. 229
Telomere Microdensitometric Scanning	p. 230
Computer Graphics Image Processing	p. 230
Microdensitometric Analysis of T-banded Human and CHo Chromosomes	p. 231
Differential Distribution of the Highest Chromatin Densities Between Sister Telomeres	p. 231
Minute Telomeric Sister-Chromatid Exchanges	p. 233
Final Remarks	p. 234
References	p. 235
Cytokinesis-Block Micronucleus Assay: a Comprehensive "Cytome" Approach for Measuring Chromosomal Instability, Mitotic Dysfunction and Cell Death Simultaneously in One Assay	p. 241
Introduction	p. 241
Nucleoplasmic Bridges	p. 244
Nuclear Buds	p. 246
Micronuclei, NPBs and Nuclear Buds Induced by Folic Acid Deficiency	p. 248
Breakage-Fusion-Bridge Cycles Explain Micronuclei, NPBs and Nuclear Buds Induced by Folic Acid Deficiency	p. 249
Micronucleus Formation Caused by Hypomethylation of Heterochromatin and Silencing of Cell Cycle Checkpoint Genes	p. 251
Conclusion	p. 252
References	p. 253
In Vivo Rodent Micronucleus Assay	p. 257
Introduction	p. 257
Historical overview	p. 259
The Rodent Micronucleus Assay for Evaluation of Chromosomal Aberration Induction of Agents	p. 260
Rodent Bone Marrow Micronucleus Assay	p. 261
Rodent Peripheral Blood Micronucleus Assay	p. 261
The Micronucleus Assay Using Tissues Other Than Bone Marrow	p. 263
Liver	p. 263
Colon	p. 264
Skin	p. 264
Testes	p. 265
Automation of the Micronucleus Assay	p. 265
Multiple End Point Assays	p. 266
References	p. 267
Sister-Chromatid Exchanges	p. 271
Introduction	p. 271
The Influence of BrdU on the Spontaneous SCE Level	p. 273
BrdU As a Source of DNA Damage Leading to SCE Formation	p. 275
The Influence of BrdU on the SCE Level Induced by Mutagenic Compounds	p. 276
The Problem of "False" and "True" SCE	p. 277
The Problem of Scoring SCEs in the Second Posttreatment Mitoses	p. 279
Conclusions	p. 280
References	p. 280
Fluorescence in Situ Hybridisation	p. 285
Introduction	p. 285
The Different Classes of DNA Probes	p. 286
Chromosome Painting Probes	p. 287
FISH Probes Composed of Repetitive DNA Sequences	p. 290
Centromere-Specific Probes	p. 290
Telomere-Specific Probes	p. 291
Locus-Specific Probes	p. 291
Comparative Genomic Hybridisation and Array Comparative Genomic Hybridisation	p. 292
Probe Labelling	p. 293
Indirect Labelling	p. 293
Direct Labelling	p. 294
The Hybridisation Procedure	p. 294
Applications	p. 295
Conclusion	p. 297
References	p. 297
The CAB and S&S Systems, and an Approach Towards the Classification of Complex Chromosome Exchanges	p. 301
Introduction	p. 301
Configuration Versus Pattern	p. 302
The CAB System	p. 304
The S&S System	p. 305
mFISH Painting	p. 306
The S&S Descriptor	p. 309
Conclusions	p. 313
References	p. 313
Aberration Patterns and Cell Cycle Progression Following Exposure of Lymphocytes to the Alkylating Agent Trenimon	p. 315
Introduction	p. 315
Methods	p. 316
Giemsa Staining	p. 316
Multicolor Fluorescence in Situ Hybridization	p. 317
Description of Aberration Types Analyzed	p. 317
Results	p. 319
Giemsa Staining	p. 319
Multicolor Fluorescence in situ Hybridization	p. 320
Conclusions	p. 322
References	p. 323
Cytogenetic Analysis and Occupational Health	p. 325
introduction	p. 325
History	p. 326
Standard Method	p. 327
Chromosomal Aberrations and Maximum Allowable Concentrations	p. 327
Cytogenetic Analysis and Public Health Practice	p. 328
Examples of occupational Exposures to Carcinogens	p. 331
Chemical industry	p. 331
Bis(chloromethyl) Ether, Chloromethyl Methyl Ether	p. 331
Epichlorohydrin	p. 332
Vinyl Chloride Monomer	p. 333
Petrochemical Industry	p. 333
Mining	p. 334
Ore Mining	p. 334
Soft Coal Open-Cast Mining	p. 334
Soft Coal Underground Mining	p. 335
Uranium Mining	p. 335
Health Care	p. 335
Cytostatics	p. 335
Halothane	p. 336
Microbiology	p. 336
Conclusions	p. 336
References	p. 337
Biological Dosimetry	p. 341
Introduction	p. 341
Blood Sampling and Culture Conditions	p. 342
Background Frequency of Asymmetrical and Symmetrical Chromosome Exchanges	p. 343
Dose-Response Relationships	p. 345
In Vitro and in Vivo Radiation-Induced Aberration Frequencies	p. 347
Dicentric Chromosomes or Symmetrical Translocations for Dose Estimation	p. 347
Summary	p. 348
References	p. 349
Statistical Methods for Biological Dosimetry	p. 351
Introduction	p. 351
Statistical Approach	p. 352
Dose Response Calibration Curves	p. 353
Dose Assessment in Whole-Body Exposure	p. 357
Examples of Dose Estimation	p. 362
Criticality	p. 362
Low Dose Overexposure	p. 363
Partial Body Exposure	p. 365
Protracted and Fractionated Exposure	p. 367
Summary	p. 368
References	p. 369
Retrospective Biological Dosimetry by FISH	p. 371
Introduction	p. 371
Method	p. 372
Which Chromosomes To Paint?	p. 372
what To Score	p. 373
Control Levels	p. 374
Persistence of Translocations	p. 375
Calibration	p. 376
Sensitivity	p. 377
Conclusion	p. 378
References	p. 378
Chromosomal Aberrations in Astronauts	p. 381
Introduction	p. 381
Measured Yields of Exchanges in the Peripheral Blood Lymphocytes of Astronauts	p. 383
Biologically Based Risk Estimates	p. 385
Cytogenetic Signatures of Space Radiation Exposure	p. 387
Persistence of Space Radiation Induced Cytogenetic Damage	p. 388
Methodology Considerations and Suggestions for Standardized Protocols	p. 391
Collection of Chromosome Samples	p. 391
Assessment of Chromosome Damage	p. 392
Dose Limitations	p. 393
Individual Sensitivity	p. 393
Dose Estimations	p. 394
Influence of Repeat Flights	p. 394
Conclusions	p. 395
References	p. 395
Internet Information System and Literature Databaseon Biomedical Activities of Electromagnetic Fields: Cancer and Cytogenetic Effects	p. 397
Introduction	p. 397
Classification of Publications	p. 398
Physical Properties	p. 398
Medical/Biological Discrimination	p. 400
The EMF-Portal: Internet Information System on the Effects of Electromagnetic Fields	p. 401
Literature Database - the Principal Item	p. 402
How to Find a Publication?	p. 402
An Example on the Subject of "Genotoxicity/Cancer"	p. 405
Discussion	p. 408
References	p. 409
Interpreting Studies on Magnetic Fields and the Risk of Childhood Leukaemia: an Ongoing Challenge	p. 411
Introduction	p. 411
Leukaemia in Children	p. 412
Description of Epidemiology and Biological Heterogeneity	p. 412
Origins of Childhood Leukaemia	p. 414
Aetiology of Childhood Leukaemia	p. 416
Exposure to Magnetic Fields and the Risk of Childhood Leukaemia	p. 418
Summary of the Epidemiological Findings	p. 418
Interpreting the Empirical Association	p. 419
Methodological Artefacts	p. 419
Alternative Explanations	p. 421
A Causal Link	p. 421
Conclusions	p. 422
References	p. 424
Cytogenetic and Carcinogenic Effects of Exposure to Radiofrequency Radiation	p. 427
Introduction	p. 427
Challenges When Conducting RFR Research	p. 429
Cytogenetic Effects of RFR	p. 431
In Vitro Studies	p. 431
In Vivo Studies	p. 437
Human Studies	p. 441
DNA Strand Breaks	p. 445
In Vitro Studies	p. 445
In Vivo Studies	p. 448
Epigenetic Effects of RFR	p. 452
Cancer Studies in Animals	p. 454
Summary	p. 464
References	p. 465
Radiofrequency Radiation and Replication Studies	p. 471
Introduction	p. 471
DNA Strand Breaks	p. 472
Micronculeus Test	p. 473
Combination Studies - RFR and Other Mutagens	p. 474
Discussion	p. 476
References	p. 477
Chromosome Analysis in Cancer Patients: Applications and Limitations	p. 479
Introduction	p. 479
Methods	p. 480
Hematologic Cancers	p. 481
Myeloid Neoplasms	p. 482
Lymphoid Neoplasms	p. 484
Solid Tumors	p. 487
Molecular Cytogenetics	p. 488
Future for Cytogenetics in Cancer Investigations	p. 492
References	p. 492
Chromosomal Aberration in Peripheral Blood Lymphocytes of Healthy Subjects and Risk of Cancer	p. 495
Biological Rationale	p. 495
The Epidemiologic Approach	p. 496
Literature Review of Cohort Studies Linking CA Frequency to the Risk of Cancer	p. 497
Pooled Analysis of Published Data	p. 499
Preliminary Results and Open Issues	p. 502
Conclusion	p. 503
References	p. 503
Index	p. 505
Table of Contents provided by Publisher. All Rights Reserved.

Chromosomal Alterations

Methods, Results and Importance in Human Health

At a Glance

Hardcover

Shipping

How to return your order

Defective items

You Can Find This Book In

Other Editions and Formats

Paperback

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