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In vivo genotoxicity of 1,4-dioxane evaluated by liver and bone marrow micronucleus tests and Pig-a assay in rats
- Source :
- Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 837:8-14
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- 1,4-Dioxane, used widely as a solvent in the manufacture of chemicals and as a laboratory reagent, induced liver adenomas and carcinomas in mice and rats, and nasal tumors in rats in several long-term studies. 1,4-Dioxane has been reported to be non-genotoxic in vitro, and there is no clear conclusion concerning its in vivo genotoxicity in rodents. In the present study, we investigated the ability of 1,4-dioxane to induce micronuclei in the liver and bone marrow of rats. For the liver micronucleus test, we performed the juvenile animal method and two methods using partial hepatectomy (PH), dosing before PH or dosing after PH. We also evaluated the in vivo mutagenicity of 1,4-dioxane by Pig-a gene mutation assay using rat peripheral blood. As a result, all methods of liver micronucleus test showed an increase in the frequency of micronucleated hepatocytes by 1,4-dioxane. The dosing before PH, a suitable method for detecting structural chromosome aberration inducers, showed the clearest response for micronucleated hepatocytes induction among the three methods. This finding is consistent with a previous report that 1,4-dioxane induces mainly chromosome breakage in the liver. Negative results were obtained in the bone marrow micronucleus test and Pig-a gene mutation assay in our study. These results suggested that 1,4-dioxane is clastogenic in the liver but not genotoxic in the bone marrow of rats.
- Subjects :
- Male
0301 basic medicine
Health, Toxicology and Mutagenesis
Bone Marrow Cells
010501 environmental sciences
Pharmacology
Gene mutation
medicine.disease_cause
01 natural sciences
Dioxanes
03 medical and health sciences
Clastogen
Bone Marrow
In vivo
Genetics
medicine
Animals
Juvenile animal
0105 earth and related environmental sciences
Micronucleus Tests
Chemistry
Membrane Proteins
Chromosome Breakage
Rats, Inbred F344
Rats
030104 developmental biology
medicine.anatomical_structure
Liver
Micronucleus test
Hepatocytes
Bone marrow
Chromosome breakage
Genotoxicity
Mutagens
Subjects
Details
- ISSN :
- 13835718
- Volume :
- 837
- Database :
- OpenAIRE
- Journal :
- Mutation Research/Genetic Toxicology and Environmental Mutagenesis
- Accession number :
- edsair.doi.dedup.....d7e15693efad876b0da082995376de60