Cytotoxic and cell transforming activities of the fungicide methyl thiophanate on BALB/c 3T3 cells in vitro.

Cytotoxic and cell-transforming activities of methyl thiophanate a systemic fungicide capable of entering plant cells and thus controlling fungal diseases that have already started were studied in an in vitro medium-term (6-8 weeks) experimental model utilizing BALB/c 3T3 cells. Cells were exposed to the chemical, dissolved in dimethyl sulfoxide, in the absence or presence of an exogenous metabolizing system derived from rat livers supplemented with cofactors (S9 mix). In the absence of metabolic activation, methyl thiophanate exerted cytotoxic activity, evidenced through the formation of cell colonies, at low doses (> 10 micrograms/ml). However, the cytotoxic activity was greatly reduced by the S9 mix-induced metabolic activation of the chemical. Without bioactivation, cell-transforming potential, evidenced through the induction of transformation foci, was observable only at the highest (weakly toxic) dose employed (25 micrograms/ml). On the contrary, in the presence of metabolic activation, the cell-transforming activity was detectable at all tested doses (i.e. from 20 to 200 micrograms/ml) and it was particularly evident in a level-II transformation amplification test when the cells were allowed to perform active proliferative activity. These results, providing further information on the activity of methyl thiophanate in multistep carcinogenesis as possible genotoxic and/or co-carcinogenic agent, may contribute to better evaluate the oncogenic risk to man.

Cytotoxic activity and transformation of BALB/c 3T3 cells in vitro by the insecticide acephate.

Cytotoxic and cell transforming activity of the organophosphate insecticide acephate have been studied in an in vitro experimental model which foresees the exposure of BALB/c 3T3 cells to the chemical. The assay was performed in the presence or absence of metabolic activation system derived from phenobarbital and beta-naphthoflavone induced rats (S9-mix). Cytotoxicity of acephate was unaffected by the presence of the metabolizing fraction. Cell-transforming potential, evidenced through the induction of transformation foci, was observed at all tested doses (i.e. 100, 200 and 400 micrograms/ml) with or without exogenous bioactivation. This activity was related with cell proliferation since it was particularly evident in a level-II cell-transformation assay when the cells were allowed to perform active proliferative activity. These findings, obtained in a medium-term (6-8 weeks) test, may contribute to a better understanding of the action of acephate in the multistep carcinogenesis, proving more information on the oncogenic risk to humans.

Transformation of BALB/c 3T3 cells in vitro by the fungicides captan, captafol and folpet.

Cytotoxic and cell-transforming activities of the three fungicides, captan, captafol and folpet, have been studied in an experimental in vitro model by exposing BALB/c 3T3 cells to the chemicals with or without S-9 mix-induced bioactivation. Cytotoxicity of the three compounds was reduced in the presence of the metabolizing system. Each assayed pesticide displayed cell-transforming ability in the presence of the metabolizing system. The relative efficiency was: captafol > captan > folpet. Cell transformation was considered to be due to carcinogenesis-promoting activity. These data, obtained in a medium-term (6-8 weeks) experimental model, contribute to a better understanding of the action of the three pesticides in the multistep carcinogenesis process and provide more information concerning the oncogenic risk of these xenobiotic compounds for humans.

Cytotoxic and cell transforming effects of the insecticide, lindane (gamma-hexachlorocyclohexane) on BALB/c 3T3 cells.

Further information was gathered on the possible carcinogenic hazard associated to the exposure to the insecticide lindane (gamma-hexachlorocyclohexane). The parameters studied were the cytotoxic and cell transforming activities of the pesticide on BALB/c 3T3 cells in an in vitro experimental model system in the absence or in the presence of rat liver S-9 mix-induced metabolic activation of the chemical. Lindane did not exert cytotoxic effects at all the tested doses (ranging from 10 micrograms/ml to 200 micrograms/ml) in the absence of bioactivation. However, dose-related cytotoxic effects were observed in the presence of the metabolizing system. Furthermore, lindane showed statistically significant and dose-dependent cell transformation activity at all the tested doses (10 micrograms/ml, 50 micrograms/ml and 100 micrograms/ml ) either in the absence or in the presence of bioactivation. This activity was related with cell proliferation since it was exerted in a level-II transformation test by replating cells and allowing the amplification of the cell transforming effects of the chemical. The formation of radicals and of reactive oxygen species, resulting from the chemical metabolism, could account for lindane activity as carcinogenesis promoting agent, although contemporary genotoxic effects induced by the pesticide could not be excluded.