Genotoxic and cytotoxic effects of carbofuran and furadan® on Chinese hamster ovary (CHOK1) cells

The in vitro geno- and cytotoxicity exerted by the N-methylcarbamate pesticide carbofuran (CF) and its commercial formulation furadan® (F®) were studied in Chinese hamster ovary (CHOK1) cells by several bioassays for both genotoxicity (e.g., the sister chromatid exchange (SCE) and micronuclei (MNi) frequencies), and cytotoxicity (e.g., cell-cycle progression, mitotic index (MI), 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and neutral red (NR)). Both CF and F® activities were tested within the range of 5–100 μg/ml. CF within a 10–100 μg/ml concentration-range induced a significant dependent increase of SCE frequency and MNi over control values. At the same concentration-range, F® increased significantly the SCE frequencies over control values although in a non-dependent manner while only an enhanced frequency of MNi was found in those 50 μg/ml-treated cultures. No binucleated cytokinesis-block cells were found in 100 μg/ml F®-treated cultures. The NDI index revealed a delay in the onset of cell-division with 50 and 100 μg/ml of CF and F®, respectively. The delayed rate of nuclear division induced by 100 μg/ml of F® was higher than that induced by an equal concentration of CF. CF and F® induced both a significant concentration-dependent delay in cell-cycle progression and a decrease in the proliferative replication index within 5–100 μg/ml and 50–100 μg/ml concentration-range, respectively. Decreased cell viability was found in up to 26% and 47% in 100 μg/ml CF- and F®-treated cultures, respectively. The NR and MTT assays revealed a clear cell growth inhibition when concentrations of 50 and 100 μg/ml of either CF or F® were employed. Accordingly, the results highlight that CF by itself and F®, even in a greater extend exerts both genotoxicity and cytotoxicity in mammalian cells in culture, at least in CHOK1 cells.