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

SOLONESKI , S., GONZALEZ, M., PIAGGIO, E., APEZTEGUÍA, M., REIGOSA, M.A. AND LARRAMENDY, M. L.

MUTAGENESIS

UK Environmental Mutagen Society/Oxford University

Año: 2001 vol. 16 p. 487 - 493

0267-8357

    The in vitro cytogenetic effects exerted by the dithiocarbamate fungicide zineb and one of its commercial formulations currently used in Argentina, azzurro, were studied in whole blood human lymphocyte cultures. The genotoxicity of the fungicides was measures by analysis of the frequency of Chromosomal aberrations and sister chromatid exchanges (SCEs)and cell cycle progression assays. Both zineb and azzurro activities were tested within the range 0.1-100.0 µg/ml immediately after in vitro lymphocyte stimulation. Only concentrations of 50.0 and 100 µg/ml  zineb and azzurro induced a significant increase in SCE frecuency over control values. Furthermore, this genotoxicity appears to be correlated with its cytotoxicity, measured as cell cycle  kinetics, since both a significant delay in cell cycle progression and a significant reduction in proliferative rate index were only observed in those cultures treated with these fungicide concentration. For both chemicals, a progressive dose-related inhibition of the mitotic activity of cultures  was observed when increasing the fungicide concentration. Moreover, onlu the mitotic activity statistically differed fron control values when doses of zineb or azzurro <10µg/ml were employed. For oth fungicides the mitotic index reached the minimal value at doses of  100 µg/ml. Both products induced a significant dose-dependent increase in the number of abnormal cells, chromatid-type and chromosome-type aberration as well as in the total number of aberrations in the 0.1-100.0 µg/ml dose range. Based on these results, the evaluation of zineb as a controversial genotoxic/non-genotoxic compound for human health should be reconsidered. Instead, we demostrate that the fungicide induced large DNA alterations and Should be considered as a clastogenis mutagen.