Quantitative dose-response analysis of ethyl methanesulfonate genotoxicity in adult gpt-delta transgenic mice

• Published in: Environmental and molecular mutagenesis Vol. 55; no. 5; pp. 385 - 399
• Main Authors: Cao, Xuefei, Mittelstaedt, Roberta A., Pearce, Mason G., Allen, Bruce C., Soeteman-Hernández, Lya G., Johnson, George E., Bigger, C. Anita H., Heflich, Robert H.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.06.2014; Wiley Subscription Services, Inc
• Subjects: Animals; benchmark dose; bilinear model; Bone marrow; DNA Damage - drug effects; DNA Damage - genetics; dose-response; Dose-Response Relationship, Drug; Escherichia coli Proteins - physiology; Ethyl Methanesulfonate - toxicity; gene mutation; Genotoxicity; gpt; Hypoxanthine Phosphoribosyltransferase - genetics; Lac Operon - genetics; Male; Membrane Proteins - genetics; Mice; Mice, Inbred C57BL; Mice, Transgenic; micronucleus; Micronucleus Tests; Mutagenicity; Mutagens; Mutagens - toxicity; Mutation; Mutation - genetics; Mutation Rate; NOGEL; Pentosyltransferases - physiology; Pig-a; Reticulocytes - drug effects; Spleen - drug effects; threshold; micronucleus; gene mutation; dose-response; benchmark dose; Pig-a; gpt; threshold; bilinear model; NOGEL

The assumption that mutagens have linear dose–responses recently has been challenged. In particular, ethyl methanesulfonate (EMS), a DNA‐reactive mutagen and carcinogen, exhibited sublinear or thresholded dose‐responses for LacZ mutation in transgenic Muta™Mouse and for micronucleus (MN) frequency i...