Oxidative-stress-driven in vivo mutagenesis induced by oral administration of potassium bromate in the small intestines of gpt delta mice

Publication date: Available online 15 January 2020Source: Mutation Research/Genetic Toxicology and Environmental MutagenesisAuthor(s): Yasunobu Aoki, Yosuke Taniguchi, Michiyo Matsumoto, Michi Matsumoto, Mizuki Ohno, Kenichi Masumura, Shigeki Sasaki, Teruhisa Tsuzuki, Masayuki Yamamoto, Takehiko NohmiAbstractTumorigenesis induced by oxidative stress are recognized to be based on mutagenesis via indirect mechanism, but mechanism underlying the thresholds shown in the dose responses of oxidative-stress-induced tumorigenesis remains to be elucidated. To reveal this mechanism, we analyzed the dose responses of mutagenesis induced in gpt delta mice by the administration of potassium bromate, a typical oxidative-stress-generating agent. We supplied Nrf2-bearing mice and Nrf2-knockout (KO) mice with drinking water containing 0, 0.06, 0.2, or 0.6 g/L potassium bromate for 90 days. We analyzed the mutants induced in the small intestine. In Nrf2-bearing mice, the mutant frequency was significantly greater than in vehicle control at a dose of 0.6 g/L but not at 0.2 g/L, indicating that a practical threshold in the mutagenesis dose response induced by potassium bromate lays between 0.2 and 0.6 g/L. At 0.6 g/L, the frequencies of G-to-T transversion (a landmark mutation of oxidative stress) and G-to-A transition were significantly elevated. In Nrf2-KO mice, the total mutant frequency was also only increased at a dose of 0.6 g/L. Elevation of G-to-T transversion at this dose is...
Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - Category: Genetics & Stem Cells Source Type: research