Genotoxic and aneugenic properties of an imidazole derivative.
To contribute to a more accurate characterization of the mutagenic and aneugenic effects of thiabendazole (TBZ), a widely used antiparasitic and food preservative drug, the induction of sister chromatid exchanges (SCEs) and mitotic spindle anomalies as cytogenetic end-points were investigated. Studies were carried out in Chinese hamster ovary (CHO) cells and human peripheral blood lymphocytes. A significant dose-dependent increase in SCE frequency was observed in CHO cells with S9-Mix (P < 0.01) in the 50-100 microg ml(-1) dose-range, while in the absence of S9-Mix, an enhancement of the SCE frequency was exhibited at the highest dose (P < 0.01). In CHO-K1 cells a significant increase in mitotic spindle anomalies (P < 0.01) was observed with the highest concentration assayed reflecting the specific effect of TBZ formulation at the microtubule level. Cell proliferation kinetics (CPK) were not modified by the addition of this pharmaceutical product. In human lymphocyte cultures, exposure to 100 microg ml(-1) TBZ formulation resulted in a significant decrease of the mitotic index (MI) (P < 0.003) and changes in the replication index (RI) (P < 0.05).
Carballo
M A
MA
Citogenética y Genética Toxicológica. Departamento de Bioquímica Clínica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina. macarballo2003@yahoo.com.ar
Hick
A S
AS
Soloneski
S
S
Larramendy
M L
ML
Mudry
M D
MD
D024422:Aneugens / Q000633:toxicity*; D000818:Animals; D016466:CHO Cells; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008214:Lymphocytes; D008940:Mitotic Index; D009152:Mutagenicity Tests / Q000379:methods; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D008941:Spindle Apparatus / Q000187:drug effects*; D013827:Thiabendazole / Q000633:toxicity*
D024422:Aneugens; D013827:Thiabendazole