Simulation of mouse and rat spermatogenesis to inform genotoxicity testing using OECD test guideline 488

Publication date: August 2018Source: Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Volumes 832–833Author(s): Francesco Marchetti, Marilyn Aardema, Carol Beevers, Jan van Benthem, George R. Douglas, Roger Godschalk, Carole L. Yauk, Robert Young, Andrew WilliamsAbstractThe Organisation for Economic Co-operation and Development Test Guideline (TG) 488 for the transgenic rodent (TGR) mutation assay recommends two sampling times for assessing germ cell mutagenicity following the required 28-day exposure period: 28 + > 49 days for mouse sperm and 28 + >70 days for rat sperm from the cauda epididymis, or three days (i.e., 28 + 3d) for germ cells from seminiferous tubules (hereafter, tubule germ cells) plus caudal sperm for mouse and rat. Although the latter protocol is commonly used for mutagenicity testing in somatic tissues, it has several shortcomings for germ cell testing because it provides limited exposure of the proliferating phase of spermatogenesis when mutations are fixed in the transgene. Indeed, analysis of sperm at 28 + 3d has generated negative results with established germ cell mutagens, while the analysis of tubule germ cells has generated both positive and either negative or equivocal results. The Germ Cell workgroup of the Genetic Toxicology Technical Committee of the Health and Environmental Sciences Institute modelled mouse and rat spermatogenesis to better define the exposure history of the cell population collected ...
Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - Category: Genetics & Stem Cells Source Type: research