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Molecular and Cellular Toxicology (eBook)

An Introduction

(Autor)

eBook Download: EPUB
2014
John Wiley & Sons (Verlag)
978-1-118-52601-9 (ISBN)

Lese- und Medienproben

Molecular and Cellular Toxicology - Lesley Stanley
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Toxicology is the study of the adverse effects of chemical, physical, or biological agents on people, animals, and the environment. Toxicologists are trained to investigate, interpret, and communicate the nature of those effects. 

Over the last ten years the subject of toxicology has changed dramatically, moving from a discipline which was once firmly wedded to traditional methods to one which is keen to embrace the innovative techniques emerging from the developing fields of cell culture and molecular biology. There is an acute need for this to be reflected in a paradigm shift which takes advantage of the opportunities offered by modern developments in the life sciences, including new in vitro and in silico approaches, alternative whole organism (non-mammalian) models and the exploitation of ‘omics methods, high throughput screening (HTS) techniques and molecular imaging technologies.

This concise, accessible introduction to the field includes the very latest concepts and methodologies. It provides MSc, PhD and final year undergraduate students in pharmacy, biomedical and life sciences, as well as individuals starting out in the cosmetics, consumer products, pharmaceutical and testing industries, with everything they need to know to get to grips with the fast moving field of toxicology and the current approaches used in the risk assessment of drugs and chemicals.


Toxicology is the study of the adverse effects of chemical, physical, or biological agents on people, animals, and the environment. Toxicologists are trained to investigate, interpret, and communicate the nature of those effects. Over the last ten years the subject of toxicology has changed dramatically, moving from a discipline which was once firmly wedded to traditional methods to one which is keen to embrace the innovative techniques emerging from the developing fields of cell culture and molecular biology. There is an acute need for this to be reflected in a paradigm shift which takes advantage of the opportunities offered by modern developments in the life sciences, including new in vitro and in silico approaches, alternative whole organism (non-mammalian) models and the exploitation of omics methods, high throughput screening (HTS) techniques and molecular imaging technologies. This concise, accessible introduction to the field includes the very latest concepts and methodologies. It provides MSc, PhD and final year undergraduate students in pharmacy, biomedical and life sciences, as well as individuals starting out in the cosmetics, consumer products, pharmaceutical and testing industries, with everything they need to know to get to grips with the fast moving field of toxicology and the current approaches used in the risk assessment of drugs and chemicals.

Dr Lesley Stanley is a toxicologist with over 20 years experience in assessing the effects of chemicals on human health. Her fi rst degree was in Biochemistry from the University of Oxford and she obtained her PhD from the University of Edinburgh. Since May 2005 she has been a freelance consultant in Investigative Toxicology, while her previous experience includes three years as Head of Operations at CXR Biosciences Ltd, Dundee, and six years lecturing in Biomedical Science at De Montfort University, Leicester, as well as spells at the MRC Toxicology Unit and the National Institute of Environmental Health Sciences, North Carolina, USA. Dr Stanley was a member of the Committee on Toxicity from 2001- to 2007 and has been a member of the Hazardous Substances Advisory Committee (previously the Advisory Committee on Hazardous Substances) since 2007. She is also Deputy Chair of the Panel of the UK Register of Toxicologists.

"Overall, we consider that this book is a useful summary of current and emerging techniques in molecular toxicology." (BTS Newsletter, 1 March 2015)

Abbreviations


3Rs replacement, refinement and reduction (of the use of animals in research)
4-ABP 4-aminobiphenyl
AAF acetylaminofluorene
ADME Absorption, Distribution, Metabolism and Excretion
AFB1 aflatoxin B1
AhR arylhydrocarbon receptor
ALT alanine aminotransferase
ASO allele-specific oligonucleotide
ASPCR allele-specific polymerase chain reaction
AST aspartate aminotransferase
ATP adenosine triphosphate
AUC area under the plasma concentration–time curve
BAC bacterial artificial chromosome
BBB blood-brain barrier
BMD benchmark dose
bp base pair
BrdU bromodeoxyuridine
CAR constitutive androstane receptor
cdk cyclin-dependent kinase
cDNA copy DNA
CEBS Chemical Effects on Biological Systems
ChIP chromatin immunoprecipitation
CHO Chinese hamster ovary
CIN cervical intraepithelial neoplasia
CITCO 6-(4-chlorophenyl)-imidazo[2,1-b]thiazole-5-carbaldehyde
CLINT intrinsic clearance
CMAX maximum (plasma) concentration
CNS central nervous system
COMET Consortium for Metabonomic Toxicology
CPMP European Committee for Proprietary Medical Products
CYP cytochrome P450
DDI drug–drug interaction
DEHP diethylhexylphthalate
DEN diethylnitrosamine
DILI drug-induced liver injury
DMBA 7,12-dimethylbenz(a)anthrancene
DMN dimethylnitrosamine
DMSO dimethyl sulphoxide
EC50 concentration giving 50% of maximal effect
ECHA European Chemical Agency
ECVAM European Centre for the Validation of Alternative Methods
EFSA European Food Safety Authority
EMA European Medicines Agency
ENU ethylnitrosourea
EPA US Environmental Protection Agency
ESC embryonic stem cell
EST embryonic stem cell test
EU European Union
FABP fatty acid binding protein
FDA US Food and Drug Administration
floxed flanked with loxP sites
GC gas chromatography
GFP green fluorescent protein
γGT gamma glutamyl transpeptidase
GI gastrointestinal
GLP Good Laboratory Practice
GSH glutathione
GST glutathione S-transferase
GTP guanosine triphosphate
GWAS genome-wide association study
HCC hepatocellular carcinoma
hERG human ether-a-go-go related gene
HO-1 haem oxygenase 1
HPRT hypoxanthine phosphoribosyltransferase
HRNTM Hepatic Reductase NullTM
HTS high throughput screening
i.p. intraperitoneal
i.v. intravenous
IC50 concentration giving 50% inhibition
ICH International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use
ILSI International Life Sciences Institute
iPSC induced pluripotent stem cell
IVIVE in vitro–in vivo extrapolation
kb kilobase
kD kilo Dalton
KEGG Kyoto Encyclopedia of Genes and Genomes
KM Michaelis constant
KOW octanol-water partition coefficient
LC liquid chromatography
LC-MS/MS liquid chromatography-tandem mass spectrometry
LD50 dose giving 50% lethality
LDH lactate dehydrogenase
LOAEL lowest observed adverse effect level
LPS lipopolysaccharide
MALDI matrix-assisted laser desorption ionisation
MAPK mitogen-activated protein kinase
MDCK Madin-Darby canine kidney
MDR multidrug resistance protein
MHLW Japanese Ministry of Health, Labour and Welfare
MHRA Medicines and Healthcare Products Regulatory Agency
MIAME Minimum Information About a Microarray Experiment
MIAPE Minimum Information About a Proteomics Experiment
MNU methylnitrosourea
MOE margin of exposure
mRNA messenger RNA
MRP multi-drug resistance-associated protein
MS mass spectrometry
MTD maximum tolerated dose
NADPH nicotinamide adenine dinucleotide phosphate
NAT N-acetyltransferase
NHS UK National Health Service
NIEHS US National Institute of Environmental Health Sciences
NIH US National Institutes of Health
NMR nuclear magnetic resonance
NOAEL no observed adverse effect level
NTP US National Toxicology Programme
OECD Organisation for Economic Co-operation and Development
p.o. perioral
PAH polycyclic aromatic hydrocarbon
PAMPA Passive Artificial Membrane Permeability Assay
Papp apparent permeability
PB phenobarbital
PBBK physiologically based biokinetic
PBPK physiologically based pharmacokinetic
PBTK physiologically based toxicokinetic
PCN pregnenlonone 16α-carbonitrile
PCR polymerase chain reaction
PhIP 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine
pKa acid dissociation constant
PPARα peroxisome proliferater activated receptor α
PPD p-phenylene diamine
PXR pregnane X-receptor
QA quality assurance
QC quality control
QSAR quantitative structure–activity relationship
QSPR quantitative structure–permeability relationship
RFLP restriction...

Erscheint lt. Verlag 2.4.2014
Sprache englisch
Themenwelt Medizin / Pharmazie Gesundheitsfachberufe
Studium 2. Studienabschnitt (Klinik) Pharmakologie / Toxikologie
Naturwissenschaften Biologie Biochemie
Naturwissenschaften Biologie Mikrobiologie / Immunologie
Technik
Schlagworte Acute • advantage • APPROACHES • Biowissenschaften • Cell & Molecular Biology • Chemie • Chemistry • Discipline • firmly • Last • Life Sciences • Medical Science • Medizin • Methods • Molekularbiologie • moving • Need • New • nonmammalian models • Oldfashioned • Omics • once • Opportunities • organism • paradigm • Pharmacology & Pharmaceutical Medicine • Pharmakologie u. Pharmazeutische Medizin • Shift • silico • Subject • ten years • Toxicology • Toxikologie • Traditional • Vitro • whole • Zellbiologie • Zell- u. Molekularbiologie
ISBN-10 1-118-52601-5 / 1118526015
ISBN-13 978-1-118-52601-9 / 9781118526019
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