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The micronucleus test with peripheral reticulocytes from phenacetin-treated mice
N Higashikuni1, T Baba, T Nakamura
1Itoham Central Research Institute, Ibaraki, Japan.
Mutation Research
|February 1, 1992
Summary
The reticulocyte (RET) assay offers a viable alternative to the traditional mouse bone marrow (BM) assay for genotoxicity testing. This non-lethal method allows for sequential sampling, enhancing its utility in in vivo micronucleus tests.
Area of Science:
- Toxicology
- Genotoxicity Testing
- In Vivo Assays
Background:
- The in vivo micronucleus test is a standard genotoxicity assay.
- Traditionally, this test uses mouse bone marrow (BM) cells, requiring animal sacrifice.
Purpose of the Study:
- To evaluate the reticulocyte (RET) assay as a non-lethal alternative to the BM assay.
- To compare the sensitivity and effectiveness of the RET assay versus the BM assay using phenacetin as a test chemical.
Main Methods:
- Comparison of mouse bone marrow (BM) and reticulocyte (RET) assays.
- Administration of phenacetin at single doses (400-800 mg/kg) and double doses.
- Sampling at 24, 48, and 72 hours post-administration.
- Evaluation of micronuclei incidence in CD-1 and MS/Ae mice.
Main Results:
- The RET assay detected genotoxicity with phenacetin at 48 hours after single doses (600-800 mg/kg) and with double doses (400 mg/kg).
- The BM assay showed slightly higher sensitivity than the RET assay.
- Double treatments improved responses in both assays compared to single treatments.
- Maximum responses in the RET assay were typically observed 24 hours after the second dose.
Conclusions:
- The RET assay is a suitable alternative to the BM assay for in vivo micronucleus testing.
- The non-lethal nature of the RET assay permits sequential sampling from the same animals.
- A recommended regimen for the RET assay involves double treatments and sampling at 24 and 48 hours post-second treatment.