Genotoxicity testing of fluconazole in vivo and in vitro.
The genotoxic effects of the antifungal drug fluconazole (trade name triflucan) were assessed in the chromosome aberration (CA) test in mouse bone-marrow cells in vivo and in the chromosome aberration, sister chromatid exchange (SCE) and micronucleus (MN) tests in human lymphocytes. Fluconazole was used at concentrations of 12.5, 25.0 and 50.0 mg/kg for the in vivo assay and 12.5, 25.0 and 50.0 microg/ml were used for the in vitro assay. In both test systems, a negative and a positive control (MMC) were also included. Six types of structural aberration were observed: chromatid and chromosome breaks, sister chromatid union, chromatid exchange, fragments and dicentric chromosomes. Polyploidy was observed in both the in vivo and in vitro systems. In the in vivo test, fluconazole did not significantly increase the frequency of CA. In the in vitro assays, CA, SCE and MN frequencies were significantly increased in a dose-dependent manner compared with the negative control. The mitotic, replication and cytokinesis-block proliferation indices (CBPI) were not affected by treatments with fluconazole. According to these results, fluconazole is clastogenic and aneugenic in human lymphocytes, but these effects could not be observed in mice. Further studies should be conducted in other test systems to evaluate the full genotoxic potential of fluconazole.
Gazi University, Science Faculty, Department of Biology, Ankara, Turkey.
Deniz
D
Yüzbaşioğlu
Fatma
F
Unal
Serkan
S
Yilmaz
Hüseyin
H
Aksoy
Mustafa
M
Celik
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology / Q000633:toxicity; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D002869:Chromosome Aberrations / Q000187:drug effects*; D015725:Fluconazole / Q000494:pharmacology / Q000633:toxicity*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D015162:Micronucleus Tests / Q000379:methods; D051381:Rats; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D000935:Antifungal Agents; D015725:Fluconazole