Genotoxicity potential of 8-Cl-cyclic adenosine monophosphate assessed with cytogenetic tests in vivo

Bajić, Vladan; Stanimirović, Zoran; Stevanović, Jevrosima

doi:10.1016/j.arcmed.2004.01.004

Cited by 11 publications

(5 citation statements)

References 24 publications

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“…There is no possibility for direct comparasion of these results since data regarding the ability of fumagillin to induce MN are lacking. Nevertheless, our results are in accordance with the published findings, considering the ability of other drugs and pesticides to increase the frequency of MN in PCE (Çelik et al 2003;Bajic et al, 2004;Andrighetti-Fröhner et al, 2006;Itoh et al, 2006).…”

Section: Discussionsupporting

confidence: 93%

Monitoring of mitotic index and frequency of micronuclei in evaluation of genotoxic potential of fumagillin (dicyclohexylamine) in vivo

Stevanović¹,

Stanimirović²,

Pejin³

et al. 2006

Acta vet. (Beogr.)

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Fumagillin (dicyclohexylamine) is a natural antibiotic, secreted by Aspergillus fumigatus. It is used in veterinary medicine against microsporidiosis in bees and fish, as well as in human medicine for the treatment of intestinal amebiasis, microsporidial keratoconjunctivitis and intestinal microsporidiosis due to Enterocytozoon bieneusi in patients with AIDS and other types of immunodeficiency. In this study, the genotoxicity of fumagillin was evaluated in mouse bone marrow cells using the mitotic index (MI) and micronucleus (MN) assay. Fumagillin was administered to BALB/c mice by gavage in doses of 25, 50, 75 mg/kg b.w., repeated for 7 days at 24h intervals, with water-sugar syrup as the negative control and cyclophosphamide as the positive control (40 mg/kg b.w) 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%) and with the positive control (14.78 ± 0.09). 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 the negative control (1.04 ± 0.28). These results suggest that fumagillin (dicyclohexilamine) has an antiproliferative and genotoxic potential in mammal in vivo test

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Section: Discussionsupporting

confidence: 93%

Monitoring of mitotic index and frequency of micronuclei in evaluation of genotoxic potential of fumagillin (dicyclohexylamine) in vivo

Stevanović¹,

Stanimirović²,

Pejin³

et al. 2006

Acta vet. (Beogr.)

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“…It is also important in the evaluation of toxicity studies to take into account the interspecies differences when extrapolating animal and other data to humans . In vitro testing is also not equivalent to in vivo human testing when using human and other cell cultures or bacteria such as Salmonella spp.…”

Section: Future Outlookmentioning

confidence: 99%

“…It is also important in the evaluation of toxicity studies to take into account the interspecies differences when extrapolating animal and other data to humans. 130 In vitro testing is also not equivalent to in vivo human testing when using human and other cell cultures or bacteria such as Salmonella spp. When all of the currently available information is evaluated, it is evident that fumagillin is indeed cytotoxic and mutagenic in vitro and that it has undisputed negative effects in humans such as shortterm toxicity, weight loss, and diarrhea.…”

Section: ■ Future Outlookmentioning

confidence: 99%

Fumagillin: An Overview of Recent Scientific Advances and Their Significance for Apiculture

Heever

Thompson

Curtis

et al. 2014

J. Agric. Food Chem.

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Fumagillin is a potent fungal metabolite first isolated from Aspergillus fumigatus. It is widely used in apiculture and human medicine against a variety of microsporidian fungal infections. It has been the subject of research in cancer treatments by employing its angiogenesis inhibitory properties. The toxicity of fumagillin has limited its use for human applications and spurred the development of analogues using structure-activity relationships relating to its angiogenesis properties. These discoveries may hold the key to the development of alternative chemical treatments for use in apiculture. The toxicity of fumagillin to humans is important for beekeeping, because any residues remaining in hive products pose a direct risk to the consumer. The analytical methods published to date measure fumagillin and its decomposition products but overlook the dicyclohexylamine counterion of the salt form widely used in apiculture.

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“…In addition, there could be an effect on the absorption of the drugs already consumed because ageing and various xenobiotics reduce the capacity for drug-metabolising enzymes (Ingelman-Sundberg, 2001; Bajic et al, 2004;Stanimirovic et al, 2005). Beekeepers being occupationally exposed to fumagillin may also be at genotoxic risk.…”

Section: Resultsmentioning

confidence: 97%

Evaluation of genotoxic effects of fumagillin by sister chromatide exchange and chromosomal aberration tests in human cell cultures

Stanimirović¹,

Pejin²,

Kulišić³

et al. 2007

Acta vet. (Beogr.)

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Fumagillin is a naturally secreted antibiotic of the fungus Aspergillus fumigatus. In veterinary medicine fumagillin is used against nosemosis in bees and microsporidiosis in fish. Since fumagillin is stable in honey in a honey bee hive there is a possible genotoxic risk to beekeepers and consumers of honey contaminated with this substance. The genotoxic effect of fumagillin was evaluated in sisterchromatid exchange (SCE) and chromosome aberration tests in cultured human peripheral blood lymphocytes at three concentrations (1.02, 3.07 and 9.20 _g/mL), with 1:1 water-sugar syrup as the negative control and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as the positive control. The mitotic and proliferative indices were calculated to detect the cytostatic effect of fumagillin. The results revealed that all tested concentrations of fumagillin (1.02, 3.07 and 9.20 _g/mL) significantly (p<0.001) increased the SCE frequency per cell and decreased the proliferative activity of human cultured lymphocytes which was manifested in the decrease in mitotic and proliferative indices. Significant increase (p<0.001) in aneuploidy and polyploidy was induced by medium and maximum concentrations of fumagillin. Besides, maximum concentrations of fumagillin significantly (p<0.001) increased the frequency of monitored structural aberrations of gap, break and insertion type. The results of this study demonstrate the genotoxic potential of fumagillin in vitro

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Genotoxicity potential of 8-Cl-cyclic adenosine monophosphate assessed with cytogenetic tests in vivo

Cited by 11 publications

References 24 publications

Monitoring of mitotic index and frequency of micronuclei in evaluation of genotoxic potential of fumagillin (dicyclohexylamine) in vivo

Monitoring of mitotic index and frequency of micronuclei in evaluation of genotoxic potential of fumagillin (dicyclohexylamine) in vivo

Fumagillin: An Overview of Recent Scientific Advances and Their Significance for Apiculture

Evaluation of genotoxic effects of fumagillin by sister chromatide exchange and chromosomal aberration tests in human cell cultures

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