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

摘要: 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 for LacZ mutation in transgenic Muta™Mouse micronucleus (MN) frequency CD1 mice (Gocke E Muller L [2009]: Mutat Res 678:101-107). order to explore variables establishing genotoxicity dose-responses, we characterized the of EMS using gene assays anticipated lower spontaneous mutant frequencies (MFs) than Muta™Mouse. Male gpt-delta were treated daily 28 days with 5 100 mg/kg EMS, measurements made on: (i) gpt MFs liver, lung, bone marrow, kidney, small intestine, spleen; (ii) Pig-a peripheral blood reticulocytes (RETs) total red cells. MN induction also was measured RETs. These data used calculate Points Departure (PoDs) dose responses, i.e., no-observed-genotoxic-effect-levels (NOGELs), confidence limits threshold effect levels (Td-LCIs), 10% benchmark response rates (BMDL10 s). Similar PoDs calculated from published induction. Vehicle control 13-40-fold vehicle MFs. general, had those mouse data. Our results indicate magnitude possibly shape mutagenicity responses differ between vivo models, generally detected by backgrounds.