Effect of the dithiocarbamate pesticide zineb and its commercial formulation azzurro. I. Genotoxic evaluation on cultured human lymphocytes exposed in vitro

The in vitro cytogenetic effects exerted by the dithiocarbamate fungicide z ineb and one of its commercial formulations currently used in Argentina, az zurro, were studied in whole blood human lymphocyte cultures. The genotoxic ity of the fungicides was measured by analysis of the frequency of chromoso mal aberrations and sister chromatid exchanges (SCEs) and cell cycle progre ssion assays. Both zineb and azzurro activities were tested within the rang e 0.1-100.0 mug/ml immediately after in vitro lymphocyte stimulation. Only concentrations of 50.0 and 100.0 mug/ml zineb and azzurro induced a signifi cant increase in SCE frequency over control values. Furthermore, this genot oxicity appears to be correlated with its cytotoxicity, measured as cell cy cle kinetics, since both a significant delay in cell cycle progression and a significant reduction in proliferative rate index were only observed in t hose cultures treated with these fungicide concentrations. For both chemica ls, a progressive dose-related inhibition of the mitotic activity of cultur es was observed when increasing the fungicide concentration. Moreover, only the mitotic activity statistically differed from control values when doses of zineb or azzurro <10 <mu>g/ml were employed. For both fungicides the mi totic index reached the minimal value at doses of 100 mug/ml. Both products induced a significant dose-dependent increase in the number of abnormal ce lls, chromatid-type and chromosome-type aberrations as well as in the total number of aberrations in the 0.1-100.0 mug/ml dose range. Based on these r esults, the evaluation of zineb as a controversial genotoxic/non-genotoxic compound for human health should be reconsidered. Instead, we demonstrate t hat the fungicide induces large DNA alterations and should be considered as a clastogenic mutagen.