Evaluation of genotoxic effects of fumagillin by cytogenetic tests in vivo
Abstract
Fumagillin is a naturally secreted antibiotic of the fungus Aspergillus fumigates. It is used in veterinary medicine against microsporidiosis of bees and fish. In this study, the genotoxicity of fumagillin (in the form of fumagillin dicyclohexylamine) was evaluated in mouse bone-marrow cells using the mitotic index (MI), the chromosome aberration (CA) assay, and the micronucleus (MN) test. Fumagillin was administered to BALB/c mice by gavage, at doses of 25, 50, 75 mg/kg body weight (bw), repeated for 7 days at 24-h intervals, with water-sugar syrup as a negative control and cyclophosphamide (40 mg/kg bw) as a positive control. All experimental doses of fumagillin induced a significant decrease (p < 0.001) in MI (3.47 +/- 0.04%, 3.17 +/- 0.01%, and 2.27 +/- 0.02%, respectively) in comparison with the negative control (6.00 +/- 0.01%). Fumagillin significantly (p < 0.001) increased the frequency of MN (4.98 +/- 0.35, 8.45 +/- 0.57, and 12.02 +/- 0.37, respectively) over negative control... (1.04 +/- 0.28). Significantly increased frequencies (p < 0.01 or p < 0.001) of numerical chromosomal aberrations (aneuploidies and polyploidies) and structural chromosomal aberrations such as gaps, breaks, and centric rings were observed at the highest experimental dose of fumagillin (75 mg/kg bw) compared with the negative control. However, with respect to the induction of Robertsonian translocations, both the intermediate (50 mg/kg bw) and highest (75 mg/kg bw) experimental dose caused a significant (p < 0.001) increase (7.12 +/- 0.26 and 9.00 +/- 0.10, respectively) in comparison with the negative control (0.00 +/- 0.00). Chromosomes 4 and 19 participated in these Robertsonian translocations. Regarding total cytogenetic changes, a significant increase (p < 0.001) was observed in both the intermediate dose group (17.36 +/- 1.83) and the highest dose group (59.49 +/- 1.92) compared with the negative control (7.00 +/- 1.35). These results suggest that fumagillin has genotoxic (clastogenic) potential in mammals in vivo.
Keywords:
fumagillin / genotoxicity / mitotic index (MI) / micronuclei (MN) / chromosome aberrations (CA) / Robertsonian chromosome Rb(4.19)Source:
Mutation Research-Genetic Toxicology and Environmental Mutagenesis, 2007, 628, 1, 1-10Publisher:
- Elsevier Science Bv, Amsterdam
Funding / projects:
- Ecophysiological and genetic investigations of domestic animals and bees for the purpose of increasing reproductive traits and disease resistance (RS-MESTD-MPN2006-2010-143022)
DOI: 10.1016/j.mrgentox.2006.09.014
ISSN: 1383-5718
PubMed: 17258933
WoS: 000245320900001
Scopus: 2-s2.0-33847196764
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Institution/Community
Fakultet veterinarske medicineTY - JOUR AU - Stanimirović, Zoran AU - Stevanović, Jevrosima AU - Bajić, Vladan AU - Radović, Ivica PY - 2007 UR - https://vet-erinar.vet.bg.ac.rs/handle/123456789/443 AB - Fumagillin is a naturally secreted antibiotic of the fungus Aspergillus fumigates. It is used in veterinary medicine against microsporidiosis of bees and fish. In this study, the genotoxicity of fumagillin (in the form of fumagillin dicyclohexylamine) was evaluated in mouse bone-marrow cells using the mitotic index (MI), the chromosome aberration (CA) assay, and the micronucleus (MN) test. Fumagillin was administered to BALB/c mice by gavage, at doses of 25, 50, 75 mg/kg body weight (bw), repeated for 7 days at 24-h intervals, with water-sugar syrup as a negative control and cyclophosphamide (40 mg/kg bw) as a positive control. All experimental doses of fumagillin induced a significant decrease (p < 0.001) in MI (3.47 +/- 0.04%, 3.17 +/- 0.01%, and 2.27 +/- 0.02%, respectively) in comparison with the negative control (6.00 +/- 0.01%). Fumagillin significantly (p < 0.001) increased the frequency of MN (4.98 +/- 0.35, 8.45 +/- 0.57, and 12.02 +/- 0.37, respectively) over negative control (1.04 +/- 0.28). Significantly increased frequencies (p < 0.01 or p < 0.001) of numerical chromosomal aberrations (aneuploidies and polyploidies) and structural chromosomal aberrations such as gaps, breaks, and centric rings were observed at the highest experimental dose of fumagillin (75 mg/kg bw) compared with the negative control. However, with respect to the induction of Robertsonian translocations, both the intermediate (50 mg/kg bw) and highest (75 mg/kg bw) experimental dose caused a significant (p < 0.001) increase (7.12 +/- 0.26 and 9.00 +/- 0.10, respectively) in comparison with the negative control (0.00 +/- 0.00). Chromosomes 4 and 19 participated in these Robertsonian translocations. Regarding total cytogenetic changes, a significant increase (p < 0.001) was observed in both the intermediate dose group (17.36 +/- 1.83) and the highest dose group (59.49 +/- 1.92) compared with the negative control (7.00 +/- 1.35). These results suggest that fumagillin has genotoxic (clastogenic) potential in mammals in vivo. PB - Elsevier Science Bv, Amsterdam T2 - Mutation Research-Genetic Toxicology and Environmental Mutagenesis T1 - Evaluation of genotoxic effects of fumagillin by cytogenetic tests in vivo VL - 628 IS - 1 SP - 1 EP - 10 DO - 10.1016/j.mrgentox.2006.09.014 ER -
@article{ author = "Stanimirović, Zoran and Stevanović, Jevrosima and Bajić, Vladan and Radović, Ivica", year = "2007", abstract = "Fumagillin is a naturally secreted antibiotic of the fungus Aspergillus fumigates. It is used in veterinary medicine against microsporidiosis of bees and fish. In this study, the genotoxicity of fumagillin (in the form of fumagillin dicyclohexylamine) was evaluated in mouse bone-marrow cells using the mitotic index (MI), the chromosome aberration (CA) assay, and the micronucleus (MN) test. Fumagillin was administered to BALB/c mice by gavage, at doses of 25, 50, 75 mg/kg body weight (bw), repeated for 7 days at 24-h intervals, with water-sugar syrup as a negative control and cyclophosphamide (40 mg/kg bw) as a positive control. All experimental doses of fumagillin induced a significant decrease (p < 0.001) in MI (3.47 +/- 0.04%, 3.17 +/- 0.01%, and 2.27 +/- 0.02%, respectively) in comparison with the negative control (6.00 +/- 0.01%). Fumagillin significantly (p < 0.001) increased the frequency of MN (4.98 +/- 0.35, 8.45 +/- 0.57, and 12.02 +/- 0.37, respectively) over negative control (1.04 +/- 0.28). Significantly increased frequencies (p < 0.01 or p < 0.001) of numerical chromosomal aberrations (aneuploidies and polyploidies) and structural chromosomal aberrations such as gaps, breaks, and centric rings were observed at the highest experimental dose of fumagillin (75 mg/kg bw) compared with the negative control. However, with respect to the induction of Robertsonian translocations, both the intermediate (50 mg/kg bw) and highest (75 mg/kg bw) experimental dose caused a significant (p < 0.001) increase (7.12 +/- 0.26 and 9.00 +/- 0.10, respectively) in comparison with the negative control (0.00 +/- 0.00). Chromosomes 4 and 19 participated in these Robertsonian translocations. Regarding total cytogenetic changes, a significant increase (p < 0.001) was observed in both the intermediate dose group (17.36 +/- 1.83) and the highest dose group (59.49 +/- 1.92) compared with the negative control (7.00 +/- 1.35). These results suggest that fumagillin has genotoxic (clastogenic) potential in mammals in vivo.", publisher = "Elsevier Science Bv, Amsterdam", journal = "Mutation Research-Genetic Toxicology and Environmental Mutagenesis", title = "Evaluation of genotoxic effects of fumagillin by cytogenetic tests in vivo", volume = "628", number = "1", pages = "1-10", doi = "10.1016/j.mrgentox.2006.09.014" }
Stanimirović, Z., Stevanović, J., Bajić, V.,& Radović, I.. (2007). Evaluation of genotoxic effects of fumagillin by cytogenetic tests in vivo. in Mutation Research-Genetic Toxicology and Environmental Mutagenesis Elsevier Science Bv, Amsterdam., 628(1), 1-10. https://doi.org/10.1016/j.mrgentox.2006.09.014
Stanimirović Z, Stevanović J, Bajić V, Radović I. Evaluation of genotoxic effects of fumagillin by cytogenetic tests in vivo. in Mutation Research-Genetic Toxicology and Environmental Mutagenesis. 2007;628(1):1-10. doi:10.1016/j.mrgentox.2006.09.014 .
Stanimirović, Zoran, Stevanović, Jevrosima, Bajić, Vladan, Radović, Ivica, "Evaluation of genotoxic effects of fumagillin by cytogenetic tests in vivo" in Mutation Research-Genetic Toxicology and Environmental Mutagenesis, 628, no. 1 (2007):1-10, https://doi.org/10.1016/j.mrgentox.2006.09.014 . .