Historical and current perspectives on genetic toxicology, with commentary and slides on assay predictivity and shortcomings, regulatory guidance, and high-throughput screens to enhance preclinical drug safety.
The Comprehensive Guide to Genotoxicity Assessment
Fundamentals Of Genetic Toxicology In The Pharmaceutical Industry Sept 2010
1. Fundamentals of Genetic Toxicology in the Pharmaceutical Industry Prepared by: David Amacher, Ph.D, DABT www.tigertox.com
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13. Examples of Genetic Toxicology Assays CHO = Chinese Hamster Ovary, HGPRT = hypoxanthine-guanine phosphoribosyl transferase gene in CHO cells, SHE = Syrian Hamster Embryo, BALB = BALB/3T3 cell transformation assay, Comet = also called single cell gel electrophoresis (SCGE)., DNA = deoxyribonucleic acid. * ICH S2B assay ‡ Good correlation with carcinogenicity (see: Regul. Toxicol. Pharmacol. 44:83-96, 2006) † Poor correlation with carcinogenicity (see: Regul. Toxicol. Pharmacol. 44:83-96, 2006) Gene Mutations Chromosome Damage Primary DNA Damage Salmonella Mammalian Microsome (Ames) Assay * ‡ In vitro metaphase chromosomal aberrations * † Transformation Assays (BALB/c or SHE) Mouse Lymphoma TK Assay (MLA) * † In vitro micronucleus test Comet Assay for DNA strand breakage ( in vitro & in vivo ) CHO/HGPRT Assay In vivo metaphase chromosomal aberrations Alkaline Elution Assay for DNA strand breakage Transgenic Assays (e.g. Big Blue® mouse & rat, Muta™ Mouse, lacZ plasmid mouse) In vivo micronucleus test * ‡ Unscheduled DNA synthesis (UDS) ( in vitro & in vivo) . DNA covalent binding assay