Department of Morphology, UNESP São Paulo State University, Institute of Biosciences, Botucatu, SP 18618-000, Brazil.
Arch Toxicol. 2010 Feb;84(2):165-73. doi: 10.1007/s00204-009-0477-0. Epub 2009 Nov 10.
The potential promoting effect of Diuron was investigated in a mouse model of mammary and urinary bladder carcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA) and N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Four-week old female Swiss mice were allocated to five groups: Groups G1-G3 received DMBA (5 x 1.5 mg/mouse) and BBN (8 x 7.5 mg/mouse) and G4 and G5 groups received only vehicles during the first 6 weeks. At week 7, G1 and G5 groups received basal diet and G2, G3 and G4 groups were fed a diet containing Diuron at 1,250, 2,500 and 2,500 ppm, respectively, during 13 weeks. At week 20, the animals were euthanized and the gross tumors were registered. Mammary glands and urinary bladder were processed for histopathological analysis. Samples from non-tumor areas were evaluated for cell proliferation by 5-bromodeoxyuridine labeling index (BrdU-LI%) and apoptosis. Dietary treatment with Diuron at 1,250 and 2,500 ppm significantly increased BrdU-LI% (P < 0.05) and the incidence of simple/nodular urothelial hyperplasia in the urinary bladder from DMBA/BBN-initiated groups (G2 and G3 vs. G1, P < 0.02) and in the non-initiated group (G4 vs. G5, P = 0.042). Two transitional cell carcinomas were observed in the group initiated and fed Diuron 2,500 ppm (G3). In contrast, in the mammary gland, Diuron feeding for 13 weeks did not significantly alter cell proliferation and apoptosis indexes or the incidence of hyperplastic lesions or neoplasms in the DMBA/BBN-initiated groups. These findings suggest that Diuron is a promoting agent to the urinary bladder but not to the mammary gland in female Swiss mice submitted to a medium-term two-stage carcinogenesis bioassay.
本研究旨在探讨敌草隆对二甲基苯并蒽（DMBA）和 N-丁基-N-（4-羟丁基）亚硝胺（BBN）诱导的雌性瑞士小鼠乳腺和膀胱致癌作用的促进作用。将 4 周龄雌性瑞士小鼠分为 5 组：G1-G3 组接受 DMBA（5x1.5mg/只）和 BBN（8x7.5mg/只），G4 和 G5 组在最初 6 周内接受仅载体处理。在第 7 周，G1 和 G5 组接受基础饮食，G2、G3 和 G4 组分别接受含敌草隆 1250、2500 和 2500ppm 的饮食，共 13 周。在第 20 周，处死动物并记录大体肿瘤。对乳腺和膀胱进行组织病理学分析。非肿瘤区域的样本通过 5-溴脱氧尿苷标记指数（BrdU-LI%）和细胞凋亡来评估细胞增殖。在 DMBA/BBN 诱导组（G2 和 G3 与 G1 相比，P<0.05）和非诱导组（G4 与 G5 相比，P=0.042）中，敌草隆 1250 和 2500ppm 的饮食处理显著增加了 BrdU-LI%和膀胱单纯/结节性尿路上皮增生的发生率。在接受 2500ppm 敌草隆诱导和喂养的组中观察到 2 例移行细胞癌。相比之下，在乳腺中，13 周的敌草隆喂养并未显著改变细胞增殖和凋亡指数，或 DMBA/BBN 诱导组中增生病变或肿瘤的发生率。这些发现表明，敌草隆是雌性瑞士小鼠中短期两阶段致癌生物测定中膀胱的促进剂，但不是乳腺的促进剂。
