Nascimento Merielen Garcia, de Oliveira Maria Luiza Cotrim Sartor, Lima Adriano Silva, de Camargo João Lauro Viana
Núcleo de Avaliação Toxicogenética e Cancerígena (TOXICAN), Departamento de Patologia, Faculdade de Medicina, UNESP, 18618-000 Botucatu, São Paulo, Brazil.
Toxicology. 2006 Jul 5;224(1-2):66-73. doi: 10.1016/j.tox.2006.04.029. Epub 2006 Apr 27.
Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide widely used on agricultural crops such as soy, cotton and sugar cane. In a previous long-term study this herbicide exerted carcinogenic activity on the urinary bladder mucosa of male Wistar rats. In general, the genotoxic and mutagenic potentials of Diuron are considered to be negative. The present study aimed to evaluate the mode of action of Diuron on the urinary bladder mucosa of male Wistar rats. Six-week old male Wistar rats were fed pelleted Nuvilab diet mixed with Diuron at 125, 500 and 2500 ppm. As a positive control, 8.3% sodium saccharin (NaS) was fed in the diet. Preceding the sacrifice of the animals at the 20th week, urinary pH was measured and the genotoxic potential of Diuron was evaluated by the comet assay. Histological urothelial lesions in the urinary bladder and in the renal pelvis mucosa, cell proliferation/apoptosis evaluations, and scanning electron microscopy (SEM) of the urinary bladder mucosa were also performed. No DNA changes were found in urothelial or peripheral blood cells, and urinary pH was comparable to controls in all Diuron groups. In the urinary bladder urothelium, the incidence of simple hyperplasia (SH) by light microscopy was significantly increased (7/10; p<0.005) in the 2500 ppm Diuron group but not at the lower doses. By SEM, three of five animals treated with 2500 ppm Diuron showed urothelial cell necrosis and hyperplasia. In the renal pelvis, the incidence of SH was significantly increased in the Diuron 500 and 2500 ppm and in the NaS 8.3% groups. Cell proliferation was significantly increased in the Diuron 2500 ppm (p<0.05) and NaS 8.3% (p<0.05) groups. The results indicate that a high dietary concentration of Diuron is associated with urothelial necrosis and continuous regenerative cell proliferation that leads to urothelial hyperplasia.
敌草隆（3-(3,4-二氯苯基)-1,1-二甲基脲）是一种取代脲类除草剂，广泛用于大豆、棉花和甘蔗等农作物。在之前的一项长期研究中，这种除草剂对雄性Wistar大鼠的膀胱黏膜产生了致癌活性。一般来说，敌草隆的遗传毒性和诱变潜力被认为是阴性的。本研究旨在评估敌草隆对雄性Wistar大鼠膀胱黏膜的作用方式。六周龄的雄性Wistar大鼠喂食与125、500和2500 ppm敌草隆混合的Nuvilab颗粒饲料。作为阳性对照，在饲料中添加8.3%的糖精钠（NaS）。在第20周处死动物之前，测量尿液pH值，并通过彗星试验评估敌草隆的遗传毒性潜力。还对膀胱和肾盂黏膜进行了组织学尿路上皮病变检查、细胞增殖/凋亡评估以及膀胱黏膜的扫描电子显微镜（SEM）检查。在尿路上皮细胞或外周血细胞中未发现DNA变化，并且所有敌草隆组的尿液pH值与对照组相当。在膀胱尿路上皮中，2500 ppm敌草隆组通过光学显微镜观察到的单纯性增生（SH）发生率显著增加（7/10；p<0.005），但在较低剂量组未出现这种情况。通过SEM观察，2500 ppm敌草隆处理的五只动物中有三只出现尿路上皮细胞坏死和增生。在肾盂中，500和2500 ppm敌草隆组以及8.3% NaS组的SH发生率显著增加。2500 ppm敌草隆组（p<0.05）和8.3% NaS组（p<0.05）的细胞增殖显著增加。结果表明，高膳食浓度的敌草隆与尿路上皮坏死和持续的再生细胞增殖有关，进而导致尿路上皮增生。
