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The effect of aging on the repeated-dose liver micronucleus assay

BACKGROUND: The liver micronucleus (MN) assay is an effective and important in vivo test for detecting genotoxic compounds. In particular, the repeated-dose liver MN (RDLMN) assay which greatly facilitates incorporation of the liver MN assay into the general toxicity study has been developed. Useful...

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Autores principales: Shigano, Miyuki, Takasawa, Hironao, Hamada, Shuichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427953/
https://www.ncbi.nlm.nih.gov/pubmed/34503583
http://dx.doi.org/10.1186/s41021-021-00212-3
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author Shigano, Miyuki
Takasawa, Hironao
Hamada, Shuichi
author_facet Shigano, Miyuki
Takasawa, Hironao
Hamada, Shuichi
author_sort Shigano, Miyuki
collection PubMed
description BACKGROUND: The liver micronucleus (MN) assay is an effective and important in vivo test for detecting genotoxic compounds. In particular, the repeated-dose liver MN (RDLMN) assay which greatly facilitates incorporation of the liver MN assay into the general toxicity study has been developed. Usefulness of the RDLMN assay was appraised highly in the 7th International Workshops on Genotoxicity Testing (2017 in Tokyo) in that sufficient numbers and types of chemicals were studied and easy integration into the general toxicity study is preferred from the 3R’s point of view. However, it was pointed out that it is necessary to evaluate the effect of age at the start of 4-week repeated administration, since there are limited data, where only those of rats of 6 week of age at the start of administration are available. In this study, we conducted the 4-week RDLMN assay using rats of 6 and 8 weeks of age (at the start of administration) to investigate the effect of age on the liver MN inducibility. Clofibrate, a weak inducer of liver MN, was used in this study to detect the slight difference in the liver MN induction. RESULTS: The liver MN induced by clofibrate was detected in both rats of 6 and 8 weeks of age at the start of administration. However, the liver MN induction was lower in rats of 8 weeks of age compared to rats of 6 weeks of age at the start of administration. CONCLUSION: These results suggest that the liver MN inducibility decreases with age. Therefore, we recommend the use of rats of 6 weeks of age at start of administration to reliably detect the liver MN induction in the RDLMN assay.
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spelling pubmed-84279532021-09-10 The effect of aging on the repeated-dose liver micronucleus assay Shigano, Miyuki Takasawa, Hironao Hamada, Shuichi Genes Environ Short Report BACKGROUND: The liver micronucleus (MN) assay is an effective and important in vivo test for detecting genotoxic compounds. In particular, the repeated-dose liver MN (RDLMN) assay which greatly facilitates incorporation of the liver MN assay into the general toxicity study has been developed. Usefulness of the RDLMN assay was appraised highly in the 7th International Workshops on Genotoxicity Testing (2017 in Tokyo) in that sufficient numbers and types of chemicals were studied and easy integration into the general toxicity study is preferred from the 3R’s point of view. However, it was pointed out that it is necessary to evaluate the effect of age at the start of 4-week repeated administration, since there are limited data, where only those of rats of 6 week of age at the start of administration are available. In this study, we conducted the 4-week RDLMN assay using rats of 6 and 8 weeks of age (at the start of administration) to investigate the effect of age on the liver MN inducibility. Clofibrate, a weak inducer of liver MN, was used in this study to detect the slight difference in the liver MN induction. RESULTS: The liver MN induced by clofibrate was detected in both rats of 6 and 8 weeks of age at the start of administration. However, the liver MN induction was lower in rats of 8 weeks of age compared to rats of 6 weeks of age at the start of administration. CONCLUSION: These results suggest that the liver MN inducibility decreases with age. Therefore, we recommend the use of rats of 6 weeks of age at start of administration to reliably detect the liver MN induction in the RDLMN assay. BioMed Central 2021-09-09 /pmc/articles/PMC8427953/ /pubmed/34503583 http://dx.doi.org/10.1186/s41021-021-00212-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Short Report
Shigano, Miyuki
Takasawa, Hironao
Hamada, Shuichi
The effect of aging on the repeated-dose liver micronucleus assay
title The effect of aging on the repeated-dose liver micronucleus assay
title_full The effect of aging on the repeated-dose liver micronucleus assay
title_fullStr The effect of aging on the repeated-dose liver micronucleus assay
title_full_unstemmed The effect of aging on the repeated-dose liver micronucleus assay
title_short The effect of aging on the repeated-dose liver micronucleus assay
title_sort effect of aging on the repeated-dose liver micronucleus assay
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427953/
https://www.ncbi.nlm.nih.gov/pubmed/34503583
http://dx.doi.org/10.1186/s41021-021-00212-3
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