Genotoxic and aneugenic properties of an imidazole derivative

Abstract

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).

In vitro genotoxic and cytotoxic effects of ivermectin and its formulation ivomec® on Chinese hamster ovary (CHOK1) cells

“…Our present observations revealed that IVM and ivomec ® failed to accumulate mitotic cells and prolonged the average cell generation time in CHO K1 cells. Both IVM-and ivomec ® -treated CHO K1 cultures exhibited a significant decrease at 50.0-250.0 g/ml concentration-range in the mitotic index as well as in the PRI which are considered as two informative biomarkers as suggested elsewhere [34,35]. These authors pinpointed both markers as good and reliable endpoints related to cytotoxicity and cellular proliferation kinetics.…”

Assessment of cytogenetic damage in bovine peripheral lymphocytes exposed to in vitro tebuconazole-based fungicide

“…As reported by Louzada et al (2010) and Carballo et al (2006), most tumours and tumour cell lines exhibit numerical and/or structural aberrations. It is well known that some members of the fungicide class (fluconazole, myclobutanil, triadimefon, propiconazole) have been established to be carcinogens in rodents (Sun et al, 2005(Sun et al, , 2006.…”

Induction of microtubule damage in Allium cepa meristematic cells by pharmaceutical formulations of thiabendazole and griseofulvin

“…Such interaction between thiabendazole and tubulin monomers prevents the normal formation of MT arrays and the occurrence of mitotic processes mediated by MT, such as chromatid segregation and cytokinesis. Instead, the presence of multipolar spindles has been reported in animal cells exposed to thiabendazole, such as CHO cells [23,24]. Their formation by direct interference of thiabendazole with tubulin would be associated with the centrosomes.…”