The phosphorylation of histone H2AX at serine 139 (γ-H2AX) is one of the first steps of DNA damage response and its detection is widely used as a sensitive marker for DNA double-strand breaks induced by ionizing radiation or other genotoxic agents. Immuno-stained phosphorylated histone can be ...
The rodent micronucleus assay has been most widely and frequently used as a representative in vivo assay system to assess mutagenicity of chemicals, regardless of endpoint of mutagenicity. The micronucleus has been developed to assess induction of structural and numerical chromoso ...
Human peripheral lymphocytes (HPL) are non-cycling primary cells (G0 cells). They are easily collectable by venipuncture. In the presence of suitable culture media and stimulants in vitro HPL enter the cell cycle and divide mitotically. Metaphase-like stages can be arrested using the sp ...
Chromosome aberration tests are used to evaluate the clastogenicity of chemical and physical agents, that is, the capacity of these agents to cause breaks in chromosomes and produce microscopically visible fragments or structural rearrangements. Aberrations are scored in metap ...
Chromosome damage is a very important indicator of genetic damage relevant to environmental and clinical studies. Detailed descriptions of the protocols used for detection of chromosomal aberrations induced by unknown agents in vitro both in the presence or the absence of rat liver-de ...
The in vitro micronucleus assay is currently one of the most commonly used test systems for the study of genotoxic effects of chemicals. It is considered the preferred method for measuring chromosome damage as it allows the determination of both chromosomal loss and breakage. The type of chromo ...
In the past two decades comparative genomic hybridization (CGH) and array CGH have become crucial and indispensable tools in clinical diagnostics. Initially developed for the genome-wide screening of chromosomal imbalances in tumor cells, CGH as well as array CGH have also been employed ...
In recent years, cytogenetics in combination with molecular methods has made rapid progress, resulting in new molecular cytogenetic methodologies such as fluorescence in situ hybridization (FISH). FISH is a molecular cytogenetic technique used for the detection of specific chro ...
During the last two decades the micronucleus (MN) test has been extensively used as a genotoxicity screening tool of chemicals and in a variety of exploratory and mechanistic investigations. The MN is a biomarker for chromosomal damage or mitotic abnormalities, since it can originate from c ...
The micronucleus (MN) assay, applied in different surrogate tissues, is one of the best validated cytogenetic techniques for evaluating chromosomal damage in humans. The cytokinesis-block micronucleus cytome assay (CBMNcyt) in peripheral blood lymphocytes is the most frequent ...
Transgenic mutation assays are used to identify and characterize genotoxic hazards and for determining the mode of action for carcinogens. The three most popular transgenic mutational models are Big Blue� (rats or mice), Muta™ mouse (mice), and gpt-delta (rats or mice). The Big Blue� and Muta™ mou ...
Assays for in vivo mutation are used to identify genotoxic hazards and phenotypes prone to genomic instability and cancer. The hypoxanthine guanine phosphoribosyl transferase (Hprt) gene and the phosphatidyl inositol glycan, class A (Pig-a) gene are endogenous X-linked genes that can ...
In addition to chromosomal damage, assessment of gene mutation is an important part of genotoxicity testing employed during preclinical safety testing. The Pig-a gene mutation assay is based on the loss of function of the Pig-a gene, which results in a lack of cell surface expression of specific p ...
The in vitro mouse lymphoma assay (MLA) is one of the most widely practiced assays in genetic toxicology. MLA detects forward mutations at the thymidine kinase (Tk) locus of the L5178Y (Tk +/− -3.7.2C) cell line derived from a mouse thymic lymphoma. This assay is capable of detecting a wide range of genetic e ...
Bacterial mutagenicity tests, specifically the Salmonella and E. coli reverse mutation (Ames) test, are widely used and are usually required before a chemical, drug, pesticide, or food additive can be registered for use. The tests are also widely used for environmental monitoring to detect m ...
Implementing pharmacogenetics in daily clinical practice has the potential to improve patient care. The translation of results of pharmacogenetic studies into practical pharmacotherapeutic recommendations is essential. These recommendations are preferably avail ...
In this chapter, we use calculation of estimated warfarin maintenance dosage as an example to illustrate how to develop a multiple linear regression model to quantify the relationship between several independent variables (e.g., patients’ genotype information) and a dependent vari ...
Pharmacogenomics studies how the variations of the individuals’ genetic makeup are correlated with a person’s response to certain drugs in relation to the therapeutic efficiency, clinical outcome, or even survival, and how they affect drug metabolism, transport, or clearance. Yet, si ...
The Pharmacogenomics Knowledge Base, PharmGKB, is an interactive tool for researchers investigating how genetic variation affects drug response. The PharmGKB Web site, http://www.pharmgkb.org, displays genotype, molecular, and clinical knowledge integrated into pathway ...
Human genomics research has produced vast amounts of data that can be applied to or used to inform pharmacogenomic studies. The Internet is an extremely useful resource for pharmacogenomics as many Web sites provide access to data from genomic and clinical studies or host tools which can be used to ...