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The micronucleus test of benzo[a]pyrene with mouse and rat peripheral blood reticulocytes
1Developmental Research Laboratory of Daiiauchi Pharmaceutical Co., Ltd., Tokyo, Japan.
Abstract:
The micronucleus test using peripheral blood reticulocytes (RETs) was evaluated in CD-1 and BDF1 mice and Sprague-Dawley rats treated with benzo[a]pyrene at two independent laboratories. The maximum incidence of micronucleated reticulocytes (MNRETs) appeared in both strains of mice 48 h after the treatment; interlaboratory differences were small. The incidence of MNRETs in BDF1 mice was higher than in CD-1 mice. In rats, significant increases of MNRETs with the maximum response at 72 h were detected when B[a]P was administered i.p.; slight but significant increases were observed at 24 h or later, with the maximum at 24-48 h, when it was administered p.o. These results suggest that the new method for the micronucleus test using circulating RETs will be useful in the detection of the clastogenicity of chemicals.
Insights
This study validated a new micronucleus test using peripheral blood reticulocytes (RETs) for detecting chemical clastogenicity. The test showed reliable results across different animal models and laboratories, confirming its utility in genotoxicity assessment.
Area of Science:
- Toxicology
- Genetics
Background:
- The micronucleus test is a standard method for assessing genotoxicity.
- Peripheral blood reticulocytes (RETs) offer a dynamic cell population for in vivo genotoxicity testing.
Purpose of the Study:
- To evaluate the efficacy and reproducibility of a peripheral blood reticulocyte micronucleus test (MNRETs).
- To assess the clastogenic potential of benzo[a]pyrene (B[a]P) in mice and rats using this method.
Main Methods:
- CD-1 and BDF1 mice, and Sprague-Dawley rats were treated with benzo[a]pyrene.
- Peripheral blood samples were analyzed for micronucleated reticulocytes (MNRETs) at various time points.
- The study was conducted across two independent laboratories to assess interlaboratory variability.
Main Results:
- The highest incidence of MNRETs in mice occurred 48 hours post-treatment, with minimal interlaboratory differences.
- BDF1 mice exhibited a higher MNRETs incidence compared to CD-1 mice.
- In rats, intraperitoneal B[a]P administration showed maximum MNRETs at 72 hours, while oral administration resulted in significant increases at 24-48 hours.
Conclusions:
- The peripheral blood reticulocyte micronucleus test is a sensitive and reproducible method for detecting chemical clastogenicity.
- This assay is valuable for genotoxicity testing across different species and administration routes.
- The findings support the use of this method for regulatory toxicology assessments.