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Evaluation of genotoxic effects of fumagillin by cytogenetic tests in vivo
- Source :
- Mutation Research-Genetic Toxicology and Environmental Mutagenesis
- Publication Year :
- 2007
- Publisher :
- Elsevier Science Bv, Amsterdam, 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.
- Subjects :
- Male
0106 biological sciences
Robertsonian chromosome Rb(4.19)
Mitotic index
Health, Toxicology and Mutagenesis
Bone Marrow Cells
Biology
Microsporidiosis
medicine.disease_cause
01 natural sciences
Chromosome aberration
Andrology
Toxicology
Mice
03 medical and health sciences
Cyclohexanes
mitotic index (MI)
Mitotic Index
Genetics
medicine
Animals
Fumagillin
030304 developmental biology
Chromosome Aberrations
Mice, Inbred BALB C
0303 health sciences
chromosome aberrations (CA)
Micronucleus Tests
genotoxicity
micronuclei (MN)
medicine.disease
fumagillin
Anti-Bacterial Agents
3. Good health
010602 entomology
Toxicity
Micronucleus test
Fatty Acids, Unsaturated
Female
Micronucleus
Sesquiterpenes
Genotoxicity
DNA Damage
medicine.drug
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Mutation Research-Genetic Toxicology and Environmental Mutagenesis
- Accession number :
- edsair.doi.dedup.....864137cfd866d1c8d0682a60e309bcdd