Effect of dithiocarbamate pesticide zineb and its commercial formulation, azzurro. III. Genotoxic evaluation on Chinese hamster ovary (CHO) cells.
The in vitro genotoxicity exerted by the dithiocarbamate fungicide zineb, and its commercial formulation azzurro, were studied in Chinese hamster ovary (CHO) cells by the analysis of the sister chromatid exchange (SCE), cell-cycle progression and single cell gel electrophoresis (SCGE) assays. Both zineb and azzurro activities were tested within the range of 0.1-100.0 microg/ml. Concentrations of 0.1-25.0 microg/ml of zineb or azzurro induced a significant dose-dependent increase in SCE frequency over control values. For both test compounds, while doses ranging from 0.1 to 1.0 microg/ml did not alter the rate of cell proliferation, a significant delay in cell-cycle progression was observed within the 5.0-25.0 microg/ml dose-range. A regression test showed that either the proliferative replication index or the mitotic activity of cultures decreased as a function of the pesticide concentration within the 1.0-25.0 microg/ml dose-range. Doses higher than 50.0 microg/ml were cytotoxic. SCGE assay revealed an increase in zineb-induced DNA damage by enhancing the proportion of slightly damaged cells in the 25.0-100.0 microg/ml dose-range and by increasing in a dose-dependent manner the proportion of damaged cells within the 1.0-100.0 microg/ml dose-range. Overall, image analysis showed statistically significant positive relationships between zineb concentration and DNA damage (expressed by image length and width) and between length and width of the damaged cells. In azzurro-treated cells, only when 100.00 microg/ml was employed a significant increase in the frequency of damaged cells over control values affecting the totality of the cells was observed only when 100.0 microg/ml was employed. When lower doses were employed, no DNA damage was revealed. Based on these results, the evaluation of zineb as a genotoxic/non-genotoxic compound for human health should be reconsidered. Even though we demonstrate that the pesticide induces large DNA alterations in vitro, does no necessarily mean that the chemical should be considered clastogenic.notoxic
Soloneski
Sonia
S
Laboratorio de Citogenética, Cátedra de Citología, Facultad de Ciencias Naturales y Museo, Universidad Nacional de La Plata, La Plata, Argentina.
González
Marina
M
Piaggio
Eduardo
E
Reigosa
Miguel A
MA
Larramendy
Marcelo L
ML
D000818:Animals; D016466:CHO Cells; D002453:Cell Cycle / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004586:Electrophoresis / Q000379:methods; D005659:Fungicides, Industrial / Q000633:toxicity; D006801:Humans; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D012854:Sister Chromatid Exchange / Q000187:drug effects; D015038:Zineb / Q000633:toxicity*
D005659:Fungicides, Industrial; D009153:Mutagens; D015038:Zineb