Cytotoxic and cell transforming activities of the fungicide methyl thiophanate on BALB/c 3T3 cells in vitro
Cytotoxic and cell transforming activities of the fungicide methyl thiophanate on BALB/c 3T3 cells in vitro
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DOI：
10.1016/s1383-5718(97)00120-4
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发表时间：
1997-11-27
影响因子：
1.9
通讯作者：
Cantelli-Forti, G
中科院分区：
文献类型：
--
作者：
Perocco, P;Del Ciello, C;Cantelli-Forti, G
利用BALB/c 3 T3细胞，在体外中期（6-8周）实验模型中研究了甲基硫菌灵的细胞毒性和细胞转化活性，甲基硫菌灵是一种能够进入植物细胞并因此控制已经开始的真菌病害的内吸性杀真菌剂。在不存在或存在补充有辅因子（S9混合物）的大鼠肝脏来源的外源性代谢系统的情况下，将细胞暴露于溶于二甲基亚砜中的化学品。在不存在代谢活化的情况下，甲基硫菌灵在低剂量（> 10 μ g/ml）下表现出细胞毒性活性，这可通过细胞集落的形成得到证明。然而，S9混合物诱导的化学品代谢活化大大降低了细胞毒活性。在没有生物活化的情况下，通过诱导转化灶证明的细胞转化潜力仅在所用的最高（弱毒性）剂量（25 μ g/ml）下可观察到。相反，在存在代谢活化的情况下，在所有试验剂量（即20 - 200 μ g/ml）下均可检测到细胞转化活性，并且当允许细胞进行主动增殖活性时，在II级转化扩增试验中尤其明显。这些结果提供了关于甲基硫菌灵作为可能的遗传毒性和/或共致癌剂在多步致癌作用中的活性的进一步信息，可能有助于更好地评估对人类的致癌风险。
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 mu g/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 mu g/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 mu g/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. (C) 1997 Elsevier Science B.V.