In vivo positive mutagenicity of 1,4-dioxane and quantitative analysis of its mutagenicity and carcinogenicity in rats

Archives of Toxicology
Min GiShoji Fukushima

Abstract

1,4-Dioxane is a widely used synthetic industrial chemical and its contamination of drinking water and food is a potential health concern. It induces liver tumors when administered in the drinking water to rats and mice. However, the mode of action (MOA) of the hepatocarcinogenicity of 1,4-dioxane remains unclear. Importantly, it is unknown if 1,4-dioxane is genotoxic, a key consideration for risk assessment. To determine the in vivo mutagenicity of 1,4-dioxane, gpt delta transgenic F344 rats were administered 1,4-dioxane at various doses in the drinking water for 16 weeks. The overall mutation frequency (MF) and A:T- to -G:C transitions and A:T- to -T:A transversions in the gpt transgene were significantly increased by administration of 5000 ppm 1,4-dioxane. A:T- to -T:A transversions were also significantly increased by administration of 1000 ppm 1,4-dioxane. Furthermore, the DNA repair enzyme MGMT was significantly induced at 5000 ppm 1,4-dioxane, implying that extensive genetic damage exceeded the repair capacity of the cells in the liver and consequently led to liver carcinogenesis. No evidence supporting other MOAs, including induction of oxidative stress, cytotoxicity, or nuclear receptor activation, that could contribut...Continue Reading

References

Aug 1, 1990·Cancer Letters·K T Kitchin, J L Brown
Aug 1, 1994·Mutation Research·A F McFeeM D Shelby
Aug 1, 1994·Mutation Research·H Tinwell, J Ashby
Dec 13, 2000·Mutation Research·T NohmiK Masumura
Apr 18, 2002·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·G G GibsonW El-Sankary
Apr 30, 2003·Environmental and Molecular Mutagenesis·Hiroyuki HayashiTakehiko Nohmi
Oct 11, 2003·Regulatory Toxicology and Pharmacology : RTP·Julie A StickneySteven F Olp
Jan 23, 2004·Toxicological Sciences : an Official Journal of the Society of Toxicology·Samuel M CohenDorothy Patton
Jul 30, 2004·Toxicological Sciences : an Official Journal of the Society of Toxicology·Manabu HoshiShoji Fukushima
Jan 22, 2005·Nature Reviews. Cancer·Andreas Luch
Mar 22, 2006·Oncogene·C Rodriguez-Antona, M Ingelman-Sundberg
Nov 23, 2006·Critical Reviews in Toxicology·Alan R BoobisWilliam Farland
Nov 28, 2006·Nature Reviews. Cancer·Daniel W Nebert, Timothy P Dalton
Oct 16, 2007·Journal of Biochemical and Molecular Toxicology·Leslie M Tompkins, Andrew D Wallace
Aug 18, 2009·Inhalation Toxicology·Tatsuya KasaiShoji Fukushima
Aug 26, 2009·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Hirokazu KanoShoji Fukushima
Nov 26, 2009·Toxicology·Gareth J S JenkinsShareen H Doak
Nov 26, 2010·British Journal of Pharmacology·Richard Maurice Walmsley, Nicholas Billinton
Sep 8, 2012·Advances in Experimental Medicine and Biology·Bilian Jin, Keith D Robertson
Sep 19, 2012·Environmental and Molecular Mutagenesis·B B GollapudiV Thybaud
May 9, 2015·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·James T MacGregorGeorge E Johnson
May 14, 2016·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Takeshi MoritaMasamitsu Honma
Jan 1, 2015·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·Kenichi MasumuraTakehiko Nohmi
Feb 9, 2017·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·Takehiko NohmiNaomi Toyoda-Hokaiwado
May 10, 2017·Environmental and Molecular Mutagenesis·Nimrat Chatterjee, Graham C Walker
Mar 9, 2018·Critical Reviews in Toxicology·Lynne T HaberAlan R Boobis
Jan 24, 2017·EFSA Journal·UNKNOWN EFSA Scientific CommitteeJosef R Schlatter

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Citations

May 12, 2020·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Yukari TotsukaHitoshi Nakagama
Jul 16, 2019·The Science of the Total Environment·Krystal J Godri PollittVasilis Vasiliou
Nov 16, 2020·Regulatory Toxicology and Pharmacology : RTP·Mark LafranconiRichard Pleus
Mar 12, 2021·Toxicological Sciences : an Official Journal of the Society of Toxicology·Georgia CharkoftakiVasilis Vasiliou
Jan 14, 2022·Journal of Toxicology and Environmental Health. Part a·Fatma Turna Demir

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Methods Mentioned

BETA
chromosomal aberrations
transgenic
PCR
Assay

Software Mentioned

GraphPad
Prism
Benchmark Dose Software ( BMDS
PROAST
BMDS

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