Publication Date:
2021-09-13
Description:
The repeated-dose liver micronucleus (RDLMN) assay is a novel method for detecting genotoxic chemicals. Two carcinogens methyl carbamate (MC) and 1, 3-propane sultone (PS) were evaluated for the liver micronucleus in a 14-day repeated-dose study with Sprague Dawley rats. Additionally, micronucleated reticulocytes (MN-RET) in peripheral blood and DNA damage (alkaline comet assay) in the liver were also assessed in the same animals. Ten groups of 5 male Sprague Dawley rats were treated once daily with MC (300, 600, or 1200 mg/kg/day), PS (37.5, 75, or 150 mg/kg/day), negative control, or 3 positive controls by oral gavage for 15 days. Blood samples were collected at 3 hours after the last administration for determining MN-RET frequencies (%MN-RET), and the livers were sampled for determining the frequency of micronuclei and DNA damage. MC was negative in the comet assay, liver micronucleus assay, and reticulocyte micronucleus assay, while PS was positive in all three assays. These results are consistent with the previous genotoxic findings of MC and PS. Therefore, the liver micronucleus assay can be effectively integrated into repeated dose studies in animals. Moreover, integration of multiple genotoxicity endpoints into one study can reduce the number of animals, boost the experimental efficiency, and provides a comprehensive evaluation of the genotoxic potential of chemicals.
Print ISSN:
0267-8357
Electronic ISSN:
1464-3804
Topics:
Biology
,
Medicine
Permalink