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Mutagenic properties of dimethylaniline isomers in mice as evaluated by comet, micronucleus and transgenic mutation assays
BACKGROUND: The carcinogenic potential of dimethylaniline (DMA) isomers in rodents and humans has been previously reported, and there is sufficient evidence for the carcinogenicity of 2,6-DMA in experimental animals. The target organ of carcinogenesis of 2,6-DMA is the nasal cavity. In the current s...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6103965/ https://www.ncbi.nlm.nih.gov/pubmed/30151062 http://dx.doi.org/10.1186/s41021-018-0106-3 |
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author | Kohara, Arihiro Matsumoto, Mariko Hirose, Akihiko Hayashi, Makoto Honma, Masamitsu Suzuki, Takayoshi |
author_facet | Kohara, Arihiro Matsumoto, Mariko Hirose, Akihiko Hayashi, Makoto Honma, Masamitsu Suzuki, Takayoshi |
author_sort | Kohara, Arihiro |
collection | PubMed |
description | BACKGROUND: The carcinogenic potential of dimethylaniline (DMA) isomers in rodents and humans has been previously reported, and there is sufficient evidence for the carcinogenicity of 2,6-DMA in experimental animals. The target organ of carcinogenesis of 2,6-DMA is the nasal cavity. In the current study, six DMA isomers, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- and 3,5-DMA, were evaluated for mutagenic properties. RESULTS: Male ddY mice (3/group) were treated intragastrically (i.g.) with 200 mg/kg of one of the six DMAs, and a comet assay was performed on samples of bone marrow, kidney, liver and lung at 3 and 24 h after the treatment. Positive responses were observed in the kidney, liver and lungs of mice from all of the DMA treatment groups after 3 h and in the bone marrow of mice treated with either 3,4- or 3,5-DMA after 3 h; however, these effects were diminished at the 24 h time point. The micronucleus induction in the bone marrow was analysed in the same mouse at 24 h after the treatment. No induction of micronucleated polychromatic erythrocytes was observed after treatment with any of the DMAs. Male transgenic Muta™ mice (five/group) were treated i.g. with 2,5-, 2,6- or 3,5-DMA at 100 mg/kg bw weekly for 4 weeks, and the lacZ and the cII mutation frequencies were examined in the nasal cavity, liver and bone marrow at 7 days after the last treatment. Statistically significant increases in the mutation frequencies of the lacZ and/or cII genes were observed in the nasal cavity of 2,5-DMA or 2,6-DMA treated mice. Sequence analysis showed increased incidences of AT to GC and GC to TA mutations in the nasal tissues. CONCLUSIONS: These findings suggest that the carcinogenic activities of DMAs are associated with mutagenic events. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s41021-018-0106-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6103965 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-61039652018-08-27 Mutagenic properties of dimethylaniline isomers in mice as evaluated by comet, micronucleus and transgenic mutation assays Kohara, Arihiro Matsumoto, Mariko Hirose, Akihiko Hayashi, Makoto Honma, Masamitsu Suzuki, Takayoshi Genes Environ Research BACKGROUND: The carcinogenic potential of dimethylaniline (DMA) isomers in rodents and humans has been previously reported, and there is sufficient evidence for the carcinogenicity of 2,6-DMA in experimental animals. The target organ of carcinogenesis of 2,6-DMA is the nasal cavity. In the current study, six DMA isomers, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- and 3,5-DMA, were evaluated for mutagenic properties. RESULTS: Male ddY mice (3/group) were treated intragastrically (i.g.) with 200 mg/kg of one of the six DMAs, and a comet assay was performed on samples of bone marrow, kidney, liver and lung at 3 and 24 h after the treatment. Positive responses were observed in the kidney, liver and lungs of mice from all of the DMA treatment groups after 3 h and in the bone marrow of mice treated with either 3,4- or 3,5-DMA after 3 h; however, these effects were diminished at the 24 h time point. The micronucleus induction in the bone marrow was analysed in the same mouse at 24 h after the treatment. No induction of micronucleated polychromatic erythrocytes was observed after treatment with any of the DMAs. Male transgenic Muta™ mice (five/group) were treated i.g. with 2,5-, 2,6- or 3,5-DMA at 100 mg/kg bw weekly for 4 weeks, and the lacZ and the cII mutation frequencies were examined in the nasal cavity, liver and bone marrow at 7 days after the last treatment. Statistically significant increases in the mutation frequencies of the lacZ and/or cII genes were observed in the nasal cavity of 2,5-DMA or 2,6-DMA treated mice. Sequence analysis showed increased incidences of AT to GC and GC to TA mutations in the nasal tissues. CONCLUSIONS: These findings suggest that the carcinogenic activities of DMAs are associated with mutagenic events. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s41021-018-0106-3) contains supplementary material, which is available to authorized users. BioMed Central 2018-08-22 /pmc/articles/PMC6103965/ /pubmed/30151062 http://dx.doi.org/10.1186/s41021-018-0106-3 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Kohara, Arihiro Matsumoto, Mariko Hirose, Akihiko Hayashi, Makoto Honma, Masamitsu Suzuki, Takayoshi Mutagenic properties of dimethylaniline isomers in mice as evaluated by comet, micronucleus and transgenic mutation assays |
title | Mutagenic properties of dimethylaniline isomers in mice as evaluated by comet, micronucleus and transgenic mutation assays |
title_full | Mutagenic properties of dimethylaniline isomers in mice as evaluated by comet, micronucleus and transgenic mutation assays |
title_fullStr | Mutagenic properties of dimethylaniline isomers in mice as evaluated by comet, micronucleus and transgenic mutation assays |
title_full_unstemmed | Mutagenic properties of dimethylaniline isomers in mice as evaluated by comet, micronucleus and transgenic mutation assays |
title_short | Mutagenic properties of dimethylaniline isomers in mice as evaluated by comet, micronucleus and transgenic mutation assays |
title_sort | mutagenic properties of dimethylaniline isomers in mice as evaluated by comet, micronucleus and transgenic mutation assays |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6103965/ https://www.ncbi.nlm.nih.gov/pubmed/30151062 http://dx.doi.org/10.1186/s41021-018-0106-3 |
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