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Micronuclei (MN) are at present the most widely used biomarker for the detection of DNA damage at the chromosomal level in human and eukaryotic cells across many species both in vitro and in vivo. They are cellular structures which contain fragments of chromosomes or whole chromosomes that have been excluded from replicating nuclei at the late anaphase/telophase stage of mitosis. MN containing chromosome fragments are a biomarker of DNA breakage, and MN containing whole chromosomes are a biomarker of either malfunction of the centromeres or kinetochores of chromosomes or damage to the mitotic machinery required to segregate chromosomes after DNA replication. It is known that chromosomal instability detected with the MN method is causally related to a wide range of diseases, particularly to cancer.

MN tests are simple, robust and amenable to automation. Their utility in toxicology is underscored by international acceptance as tests for DNA damage in human and rodent cells caused by genotoxic chemicals and radiation and by the development of regulatory guidelines for these purposes. More than 10 000 papers on the biology of MN generally and at least 3800 scientific papers have been published in peer-reviewed journals on the use of MN assays to measure DNA damage. Our aim was to capture this wealth of knowledge on the MN assay and its application in genetic toxicology into a single reference book for use by students, lecturers, established scientists, and health professionals.

The book is divided into three sections: (i) The origins of MN and their association with diseases (four chapters); (ii) The in vitro and in vivo application of MN assays in experiments using cells from humans, rodents and other species (17 chapters) and (iii) MN assays and their application to study DNA damage induced by in vivo exposure to genotoxins in humans (17 chapters). The second section also includes information on appropriate study design, statistical analyses of MN data in various research scenarios and the current status of automated methods for scoring MN in human and rodent cells.

The unique appeal of this book is that each chapter is written by a recognised expert in the application of MN assays either in humans or rodents or in other eukaryotic species relevant to application in different ecosystems, such as MN assays in fish, amphibians, reptiles and plants. The chapters in Section 1 describe how the MN assay evolved from classical metaphase analysis of chromosomes, the molecular origins of DNA damage and defects of the mitotic machinery that lead to MN formation, the fate of cells with MN and the association of increased MN frequencies in human cells in vivo or ex vivo with infertility, pregnancy complications, developmental diseases, inflammation and age-related chronic diseases, cardiovascular and neurological diseases, premature ageing syndromes and cancer, for which the current evidence for plausibility and causality is strongest.

The chapters in Section 2 provide the most relevant aspects of the MN assay methodology that are used across a wide range of cell types and species. This includes a brief description of the biology of the cell types and why they are used in MN experiments, a succinct description of the method concerning the most critical aspects such as cell collection, and its timing relative to exposure, fixation as well as staining and scoring methods, a photo gallery of cells with MN and other nuclear anomalies accompanied by line diagrams of the cells, a description of scoring criteria, common technical problems and how to overcome them, knowledge and technological gaps that need to be addressed in the future, and references to the key papers that describe the method in greater detail for those who want to establish the assay in their laboratory.

Section 3 includes a selection of papers that systematically review the results of the application of the MN assay to measure DNA damage in humans exposed occupationally or via their lifestyle to a wide range of genotoxins (e.g. heavy metals, industrial organic chemicals, cytotoxic drugs, coal dust, asbestos, pesticides, ionising and non-ionising radiation, tobacco, etc.) and critically identify the strength and weaknesses of currently available data. Meta-analyses of previous studies are reported depending on the quality and heterogeneity of study design.

The purpose of this book is to provide a strong foundation to further improve the MN assay and broaden its application by using the emerging cytome approaches that include additional biomarkers such as nucleoplasmic bridges and nuclear buds as well centromere detection in MN that complement the conventional MN assays. These novel ancillary biomarkers and their close mechanistic relationship with MN are described in some of the chapters in the book.

The deeper understanding of the MN assay that this book provides should stimulate the evolution of better application of MN assays across species for the detection of genotoxic agents in the environment and to define their dose–response characteristics (independently or interactively with other factors such as genotype, co-exposure with other genotoxins, nutritional deficiency or excess).

The editors are very thankful to all of the authors of the chapters in this book for the dedication of their time to this important endeavour. We are also grateful to Armen Nersesyan for assisting with the review of chapters contributed to this book. Finally, we appreciate very much working with the Royal Society of Chemistry via their Commissioning Editors Rowan Frame and Robin Driscoll and Editorial Assistant Katie Morrey, without whom this book could not have been realised.

Siegfried Knasmüller and Michael Fenech

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