Abstract
BackgroundThe 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.ResultsThe 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.ConclusionThese 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.
Highlights
The liver MN assay is useful to evaluate the genotoxic potential to induce chromosome aberration in the liver
The repeated-dose liver MN (RDLMN) assay has been developed well in the Mammalian Mutagenicity Study Group (MMS) in the Japanese Environmental Mutagen Society (JEMS) because it could be incorporated into the general toxicity study
In the Collaborative Study Group for the Micronucleus Test (CSGMT) of JEMS/mammalian mutagenicity study group (MMS), 22 carcinogens were evaluated in the RDLMN assay, in which hepatocarcinogens showed a
Summary
The liver MN assay is useful to evaluate the genotoxic potential to induce chromosome aberration in the liver. The repeated-dose liver MN (RDLMN) assay has been developed well in the Mammalian Mutagenicity Study Group (MMS) in the Japanese Environmental Mutagen Society (JEMS) because it could be incorporated into the general toxicity study. In the Collaborative Study Group for the Micronucleus Test (CSGMT) of JEMS/MMS, 22 carcinogens were evaluated in the RDLMN assay, in which hepatocarcinogens showed a Shigano et al Genes and Environment (2021) 43:37 described above used only rats of 6 weeks of age at the start of administration. The repeated-dose liver MN (RDLMN) assay which greatly facilitates incorporation of the liver MN assay into the general toxicity study has been developed. 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
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