Scassellati-Sforzolini G, Pasquini R, Moretti M, Villarini M, Fatigoni C, Dolara P, Monarca S, Caderni G, Kuchenmeister F, Schmezer P, Pool-Zobel B L
Department of Hygiene, University of Perugia, Italy.
Mutat Res. 1997 May 23;390(3):207-21. doi: 10.1016/s1383-5718(97)00012-0.
The ureic herbicide linuron [3-(3, 4-dichlorophenyl)-1-methoxy-1-methylurea] (CAS 330-55-2) was investigated for genotoxicity in a series of in vivo experiments. Since human exposure to herbicides is not only to the active principles, but also to all the chemicals present in the commercial formulation, we tested both pure and commercial linuron. Groups of rats were treated with gavage containing different doses of the herbicide (pure compound or commercial formulation) for 14 days. The doses were 150, 300 and 450 mg/kg b.wt. for the pure compound and 315.8, 631.6 and 947.4 mg/kg b.wt. for the commercial formulation (47.5% of linuron). Faeces and urine were collected at regular intervals. Urine specimens were analysed for their mutagenic metabolites, thioethers and D-glucaric acid content. Faeces extracts were tested for mutagenicity. Linuron's ability to cause DNA damage and cytogenetic effects was also investigated after treating groups of rats once with different doses of pure or commercial linuron. DNA single-strand breaks were assessed in rat liver using the alkaline elution technique and the single-cell microgel electrophoresis assay (SCGE: 'comet' assay), and in rat testes cells with the SCGE assay. Micronuclei induction was analysed in rat bone marrow erythrocytes. Results obtained were mainly negative when the excretion of mutagenic metabolites in urine and faeces of animals treated with the pure compound or with the linuron-based commercial formulation were monitored, whereas an increase in the urinary excretion of thioethers and D-glucaric acid was observed in rats treated with the commercial formulation. No increase in the frequency of micronucleated polychromatic erythrocytes was observed in the treated animals. However, linuron affected the viability of hepatocytes isolated from animals treated with higher doses. This cytotoxicity was accompanied by the induction of DNA single-strand breaks in the liver, as seen by the alkaline elution assay. The potential of pure linuron to induce in vivo DNA damage was confirmed with the microgel-electrophoresis technique ('comet' assay). Cytotoxicity was also seen in rat testes cells. However, no indication of DNA damage was visible.
在一系列体内实验中，对脲类除草剂利谷隆[3-(3,4-二氯苯基)-1-甲氧基-1-甲基脲](CAS 330-55-2)的遗传毒性进行了研究。由于人类接触除草剂不仅涉及活性成分，还包括商业制剂中存在的所有化学物质，因此我们对纯品和商业制剂利谷隆都进行了测试。用含有不同剂量除草剂（纯化合物或商业制剂）的灌胃法处理大鼠组14天。纯化合物的剂量为150、300和450毫克/千克体重，商业制剂（利谷隆含量47.5%）的剂量为315.8、631.6和947.4毫克/千克体重。定期收集粪便和尿液。分析尿液标本中的诱变代谢物、硫醚和D-葡萄糖醛酸含量。检测粪便提取物的诱变性。在用不同剂量的纯品或商业制剂利谷隆一次性处理大鼠组后，还研究了利谷隆导致DNA损伤和细胞遗传学效应的能力。使用碱性洗脱技术和单细胞微凝胶电泳分析（SCGE：“彗星”分析）在大鼠肝脏中评估DNA单链断裂，并在大鼠睾丸细胞中用SCGE分析进行评估。在大鼠骨髓红细胞中分析微核诱导情况。当监测用纯化合物或基于利谷隆的商业制剂处理的动物尿液和粪便中诱变代谢物的排泄情况时，获得的结果主要为阴性，而在用商业制剂处理的大鼠中观察到硫醚和D-葡萄糖醛酸的尿排泄增加。在处理的动物中未观察到多染性红细胞微核频率增加。然而，利谷隆影响了用较高剂量处理的动物分离的肝细胞的活力。如碱性洗脱分析所示，这种细胞毒性伴随着肝脏中DNA单链断裂的诱导。微凝胶电泳技术（“彗星”分析）证实了纯利谷隆在体内诱导DNA损伤的可能性。在大鼠睾丸细胞中也观察到了细胞毒性。然而，未发现DNA损伤的迹象。
