Chemical structure-related mechanisms underlying in vivo genotoxicity induced by nitrofurantoin and its constituent moieties in gpt delta rats

Toxicology
Aki KijimaT Umemura

Abstract

Nitrofurans are antimicrobial compounds containing a nitro group at the 5-position of the furan ring and an amine or hydrazide side chain derivative. One member of the nitrofurans, nitrofurantoin (NFT), is a renal carcinogen in male rats despite its still controversial genotoxicity. We investigated chemical structure-related modes of action of NFT, and reporter gene mutation assays for NFT and its constituent moieties were performed. NFT, 5-nitro-2-furaldehyde (NFA), or 1-aminohydantoin (AHD) was administered to male F344 gpt delta rats by gavage for 4 or 13 weeks at a carcinogenic or the maximum tolerated dose. NFT caused a significant increase in gpt mutant frequency (MF) at 13 weeks with G-base substitution mutations. An increase in gpt MF was also observed in the NFA-treated group at 13 weeks, but not in the AHD-treated group. 8-Hydroxydeoxyguanosine (8-OHdG) levels in the kidney DNA of NFT-treated rats were significantly increased after 4 weeks. NFT caused accumulation of hyaline droplets indicated by positive immunostaining and western blot analysis for α2u-globulin in the proximal tubules. An additional study, in which female gpt delta rats were given NFT at the same dose used for males, was performed to mitigate the eff...Continue Reading

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Citations

Mar 14, 2017·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Luis J A Martins, João M M Ferreira
Aug 11, 2018·Journal of Toxicologic Pathology·Takuma TsuchiyaTakashi Umemura
Feb 2, 2019·International Journal of Environmental Research and Public Health·Chia-Hung HuangChao-Bin Yeh
May 6, 2019·International Journal of Environmental Research and Public Health·Amanda PacholakEwa Kaczorek
Jan 15, 2016·The Journal of Toxicological Sciences·Masayuki KimuraMakoto Shibutani
Oct 4, 2018·Mutagenesis·Rachael E TennantRichard V Williams

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