Osaba Lourdes, Rey María Jesús, Aguirre Ana, Alonso Angeles, Graf Ulrich
Department of Animal Biology and Genetics, Sciences Faculty, University of Basque Country, E-48080 Bilbao, Spain.
Mutat Res. 2002 Jun 27;518(1):95-106. doi: 10.1016/s1383-5718(02)00080-3.
The wing spot test in Drosophila melanogaster is a suitable system for the analysis of genotoxic activity of compounds that need metabolic transformation to render them active. We have analysed the genotoxicity of three fungicides for which it was reported that the metabolic processes taking place in vivo may determine their activity. The compounds analysed are captan, maneb, zineb and ethylenethiourea (ETU) (a metabolic derivative of ethylenebisdithiocarbamates like maneb and zineb). We have also evaluated the ability of ETU to form genotoxic derivatives in vivo analysing this compound in combined treatments with sodium nitrite. Both standard and high bioactivation NORR strains have been used. Captan, usually considered a mutagen in vitro but a non-mutagen in vivo, gave negative results in the wing spot test with both crosses. Positive results were obtained for maneb in the standard cross and for ETU in both the standard and the high bioactivation cross. The genotoxicities of maneb and ETU were higher when treatments were made on media in which nitrosation is favoured. A low absorption of the fungicide and an inefficient availability of the compound in the target may explain negative results obtained with zineb in both crosses. The results obtained in this study with the wing spot test demonstrate once again the suitability of this in vivo assay, in which absorption, distribution and metabolism processes take place, for the evaluation of genotoxicity of compounds to which humans are exposed.
黑腹果蝇的翅斑试验是一种适用于分析需要代谢转化才能发挥活性的化合物遗传毒性活性的系统。我们分析了三种杀菌剂的遗传毒性，据报道，其体内发生的代谢过程可能决定它们的活性。所分析的化合物有克菌丹、代森锰、代森锌和乙撑硫脲（ETU）（代森锰和代森锌等亚乙基双硫代氨基甲酸盐的代谢衍生物）。我们还通过分析亚硝酸钠联合处理中的这种化合物，评估了ETU在体内形成遗传毒性衍生物的能力。使用了标准和高生物活化NORR菌株。克菌丹通常在体外被认为是诱变剂，但在体内是非诱变剂，在两个杂交组合的翅斑试验中均给出阴性结果。代森锰在标准杂交组合中呈阳性结果，ETU在标准和高生物活化杂交组合中均呈阳性结果。当在有利于亚硝化作用的培养基上进行处理时，代森锰和ETU的遗传毒性更高。杀菌剂的低吸收以及化合物在靶标中的低效可用性可能解释了代森锌在两个杂交组合中获得的阴性结果。本研究通过翅斑试验获得的结果再次证明了这种体内试验的适用性，该试验中发生吸收、分布和代谢过程，可用于评估人类接触的化合物的遗传毒性。
