Doi: 10.2298/avb0604353s Udk 619:615.035.2 Frequency of Chromosomal Aberrations in the Evaluation of Genotoxic Potential of Dicyclohexylamine (fumagillin) in Vivo

Dicyclohexylamine (fumagillin), as an antibiotic produced by fermentation of Aspergillus fumigatus, is used in human medicine for the treatment of intestinal microsporidiosis in patients with HIV infection, intestinal amebiasis and microsporidial keratoconjunctivitis. In veterinary medicine, fumagillin is effective in suppressing microsporidiosis of bees and fish. In this study, the genotoxicity of fumagillin was evaluated in mouse bone marrow cells using chromosome aberrations (CA) assay. Dicyclohexylamine was administered to mice by gavage in a dose of 25, 50, 75 mg/kg b.w., with water-sugar syrup as the negative control and cyclophosphamide as the positive control (40 mg/kg b.w.) Significantly increased frequency (p<0.01 or p<0.001) of numerical chromosomal aberrations (aneupliodies and polyploidies) and structural chromosomal aberrations of gaps, breaks and centric rings were observed only at the highest experimental dose of dicyclohexylamine, compared with the negative control. However, in point of induction of Rb translocations, both the median (50 mg/kg b.w.) and highest (75 mg/kg b.w.) experimental dose showed a significant (p<00.001) 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 Rb translocations. These results suggest that dicyclohexilamine (fumagillin) has genotoxic potential in mammal in vivo chromosomal aberration (CA) test system.