Grassi Tony Fernando, Tararam Cibele Aparecida, Spinardi-Barbisan Ana Lúcia Tozzi, Domingues Maria Aparecida Custódio, de Camargo João Lauro Viana, Barbisan Luís Fernando
School of Medicine, Department of Pathology, UNESP São Paulo State University, Botucatu, SP, Brazil.
Toxicol Pathol. 2007 Dec;35(7):897-903. doi: 10.1080/01926230701748040.
The promoting activity of the herbicide Diuron was evaluated in a medium-term rat liver carcinogenesis bioassay that uses as endpoint immunohistochemically identified glutathione S-transferase positive (GST-P+) foci. Male Wistar rats were allocated to the following groups: G1 to G6 were initiated for liver carcinogenesis by a single dose of diethylnitrosamine (DEN, 200 mg/kg) while groups G7 and G8 received only 0.9% NaCl (DEN vehicle). From the 2nd week animals were fed a basal diet (G1 and G7) or a diet added with Diuron at 125, 500, 1250, 2500 and 2500 ppm (G2 to G5 and G8, respectively) or 200 ppm Hexaclorobenzene (HCB; G6). The animals were submitted to 70% partial hepatectomy at the 3rd week and sacrificed at the 8th week. The herbicide did not alter ALT or creatinine serum levels. No conspicuous GST-P+ foci development was registered in non-initiated rats fed Diuron at 2500 ppm. While DEN-initiated animals fed Diuron at 1250 or 2500 ppm developed mild centrilobular hypertrophy, DEN-initiated HCB-fed animals showed severe liver centrilobular hypertrophy and significant GST-P+ foci development. These findings indicate that the medium-term assay adopted in this study does not reveal any liver carcinogenesis initiating or promoting potential of Diuron in the rat.
在一项中期大鼠肝癌发生生物测定中评估了除草剂敌草隆的促癌活性，该测定以免疫组织化学鉴定的谷胱甘肽S-转移酶阳性（GST-P+）病灶为终点。将雄性Wistar大鼠分为以下几组：G1至G6组通过单剂量二乙基亚硝胺（DEN，200 mg/kg）启动肝癌发生，而G7和G8组仅接受0.9%氯化钠（DEN溶剂）。从第2周起，动物分别喂食基础饮食（G1和G7组）或添加了125、500、1250、2500和2500 ppm敌草隆的饮食（分别为G2至G5组和G8组），或200 ppm六氯苯（HCB；G6组）。在第3周对动物进行70%部分肝切除术，并在第8周处死。该除草剂未改变血清谷丙转氨酶（ALT）或肌酐水平。在喂食2500 ppm敌草隆的未启动大鼠中未观察到明显的GST-P+病灶发展。虽然喂食1250或2500 ppm敌草隆的DEN启动动物出现轻度中央小叶肥大，但喂食HCB的DEN启动动物表现出严重的肝脏中央小叶肥大和显著的GST-P+病灶发展。这些发现表明，本研究采用的中期测定未揭示敌草隆在大鼠中有任何引发或促进肝癌发生的潜力。
