Fetal liver micronucleus assay in mice of 5-fluorouracil and related compounds |
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| Institution: | 1. School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, 14040-903 Ribeirão Preto, São Paulo, Brazil;2. National Institute of Science and Technology for Detection, Toxicological Evaluation and Removal of Micropollutants and Radioactive Substances (INCT-DATREM), Brazil;3. Faculty of Sciences, University of Lisbon, Campo Grande, 1749-016 Lisboa, Portugal;4. Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Departamento de Química, Universidade de São Paulo, Av. Bandeirantes, 3900, Bairro Monte Alegre, Ribeirão Preto, São Paulo CEP 14040901, Brazil |
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| Abstract: | The cytogenetic effects of 5-fluorouracil (5-FU), 1-hexyl-carbamoyl-5-fluorouracil (HCFU) and 1-(2-tetrahydrofuryl)-5-fluorouracil (TF) were examined with the fetal liver micronucleus assay in mice. The frequencies of micronucleated polychromatic erythrocytes (MNPCEs) in fetal liver peaked at 27, 24 and 27 h, respectively, after single intraperitonealinjections into pregnant mice on day 13 of gestation. The highest frequency of MNPCEs by 5-FU treatment in fetal liver was 13.6%, whereas the frequency in maternal bone marrow was only 0.4%. The micronucleus frequency and the number of micronuclei per individual polychromatic erythrocyte were clearly dose-dependent.These results suggest that the micronucleus test in fetal liver has particular advantages compared to maternal bone marrow for evaluating the cytogenetic effects of 5-FU and related compounds after a single treatment. The cytogenetic effect was ranked 5-FU = HCFU > TF, in both a time-course study and a dose-response study of micronucleus distribution. |
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