Identifying germ cell mutagens using OECD test guideline 488 (transgenic rodent somatic and germ cell gene mutation assays) and integration with somatic cell testing

Publication date: August 2018Source: Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Volumes 832–833Author(s): Francesco Marchetti, Marilyn J. Aardema, Carol Beevers, Jan van Benthem, Roger Godschalk, Andrew Williams, Carole L. Yauk, Robert Young, George R. DouglasAbstractThe Organisation for Economic Co-operation and Development Test Guideline 488 (TG 488) provides recommendations for assessing germ cell and somatic cell mutagenicity using transgenic rodent (TGR) models. However, important data gaps exist for selecting an optimal approach for simultaneously evaluating mutagenicity in both cell types. It is uncertain whether analysis of germ cells from seminiferous tubules (hereafter, tubule germ cells) or caudal sperm within the recommended design for somatic tissues (i.e., 28 days of exposure plus three days of fixation time, 28 + 3d) has enough sensitivity to detect an effect as compared with the analysis of sperm within the recommended design for germ cells (i.e., 28 + 49d and 28 + 70d for mouse and rat, respectively). To address these data gaps, the Germ Cell workgroup of the Genetic Toxicology Technical Committee of the Health and Environmental Sciences Institute reviewed the available TGR mutagenicity data in male germ cells, and, characterized the exposure history of tubule germ cells for different sampling times to evaluate its impact on germ cell mutagenicity testing using TG 488. Our analyses suggest that evaluating mutant frequenc...
Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - Category: Genetics & Stem Cells Source Type: research