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The 28 + 28 day design is an effective sampling time for analyzing mutant frequencies in rapidly proliferating tissues of MutaMouse animals.
Arch Toxicol
March 2021
Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, 251 Sir Frederick Banting Driveway, Ottawa, ON, K1A 0K9, Canada.
The Organisation for Economic Co-Operation and Development Test Guideline 488 (TG 488) uses transgenic rodent models to generate in vivo mutagenesis data for regulatory submission. The recommended design in TG 488, 28 consecutive daily exposures with tissue sampling three days later (28 + 3d), is optimized for rapidly proliferating tissues such as bone marrow (BM). A sampling time of 28 days (28 + 28d) is considered more appropriate for slowly proliferating tissues (e.
View Article and Find Full Text PDFChemically induced mutations in a MutaMouse reporter gene inform mechanisms underlying human cancer mutational signatures.
Commun Biol
August 2020
Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Ontario, K1A 0K9, Canada.
Transgenic rodent (TGR) models use bacterial reporter genes to quantify in vivo mutagenesis. Pairing TGR assays with next-generation sequencing (NGS) enables comprehensive mutation pattern analysis to inform mutational mechanisms. We used this approach to identify 2751 independent lacZ mutations in the bone marrow of MutaMouse animals exposed to four chemical mutagens: benzo[a]pyrene, N-ethyl-N-nitrosourea, procarbazine, and triethylenemelamine.
View Article and Find Full Text PDFIntegration of sperm DNA damage assessment into OECD test guidelines for genotoxicity testing using the MutaMouse model.
Toxicol Appl Pharmacol
October 2018
Environmental Health Science and Research Bureau, Health Canada, Tunney's Pasture, 0803A, Ottawa, ON K1A 0K9, Canada. Electronic address:
The Organisation for Economic Co-operation and Development (OECD) endorses test guidelines (TG) for identifying chemicals that are genotoxic, such as the transgenic rodent gene mutation assay (TG 488). Current OECD TG do not include assays for sperm DNA damage resulting in a critical testing gap. We evaluated the performance of the Sperm Chromatin Structure Assay (SCSA) and the Terminal Deoxynucleotidyl Transferase-Mediated Deoxyuridine Triphosphate Nick end Labeling (TUNEL) assay to detect sperm DNA damage within the recommended TG 488 protocol.
View Article and Find Full Text PDFAdaptive resistance of Saccharomyces cerevisiae to chronic treatment with genotoxic and nongenotoxic carcinogens.
J Environ Pathol Toxicol Oncol
August 2004
Department of Genetics, Fraunhofer Institute of Toxicology and Aerosol Research, Hannover, Germany.
The exposure of mammalian cells or tumors for weeks or months to low nonlethal doses of cytostatic drugs may induce multidrug resistance, which can be enhanced by a variety of DNA-damaging agents. Multidrug resistance to a variety of drugs has been observed. But in yeast, DNA-damaging agents have not yet been tested.
View Article and Find Full Text PDFRadiation- and chemical-induced structural chromosome aberrations in human spermatozoa.
Mutat Res
July 2002
Department of Biological Sciences, Asahikawa Medical College, 2-1-1-1 Midorigaoka-higashi, Asahikawa, Japan.
Previous studies on the clastogenic effects of mutagens on human sperm chromosomes were reviewed. A marked increase of structural chromosome aberrations (SCAs) has been reported in the spermatozoa irradiated in vitro with five kinds of ionizing radiation (137Cs gamma-, 60Co gamma-, X-, and 3H beta-rays and 252Cf neutrons). The micronucleus (MN) test with hybrid two-cell embryos generated from human sperm and hamster oocytes was shown to be useful as a simple and rapid method for assessing the effects of radiation.
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