کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8456181 | 1548540 | 2018 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Identifying germ cell mutagens using OECD test guideline 488 (transgenic rodent somatic and germ cell gene mutation assays) and integration with somatic cell testing
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The 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, 28â¯+â¯3d) has enough sensitivity to detect an effect as compared with the analysis of sperm within the recommended design for germ cells (i.e., 28â¯+â¯49d and 28â¯+â¯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 frequencies in: i) sperm from the cauda epididymis at 28â¯+â¯3d does not provide meaningful mutagenicity data; ii), tubule germ cells at 28â¯+â¯3d provides reliable mutagenicity data only if the results are positive; and iii) tubule germ cells at 28â¯+â¯28d produces reliable positive and negative results in both mice and rats. Thus, the 28â¯+â¯28d regimen may provide an approach for simultaneously assessing mutagenicity in somatic tissues and germ cells from the same animals. Further work is required to support the 28â¯+â¯28d protocol for tissues other than slowly proliferating tissues as per current TG 488. Finally, recommendations are provided to guide the experimental design for germ cell mutagenicity data for regulatory submission, as well as other possible approaches to increase the reliability of the TGR assay.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Mutation Research/Genetic Toxicology and Environmental Mutagenesis - Volumes 832â833, August 2018, Pages 7-18
Journal: Mutation Research/Genetic Toxicology and Environmental Mutagenesis - Volumes 832â833, August 2018, Pages 7-18
نویسندگان
Francesco Marchetti, Marilyn J. Aardema, Carol Beevers, Jan van Benthem, Roger Godschalk, Andrew Williams, Carole L. Yauk, Robert Young, George R. Douglas,