Toyoda K, Imaida K, Shirai T, Imazawa T, Takahashi M
First Department of Pathology, Nagoya City University Medical School, Japan.
J Toxicol Environ Health. 1993 May;39(1):59-78. doi: 10.1080/15287399309531736.
Dietary supplementation with bisacodyl at concentrations ranging from 1 to 0.3% was found to induce both calculi and epithelial proliferative lesions, including a transitional-cell carcinoma, in the urinary bladder of F344/DuCrj rats. In order to clarify the relationship between the bisacodyl-associated urinary bladder calculi and the development of proliferative lesions in the urinary bladder, male and female rats were administered bisacodyl-diets at concentrations of 0.3, 0.1, and 0.03% for 32 wk. Both sexes of animals treated with bisacodyl suffered from diarrhea throughout the experimental period. Epithelial proliferative lesions and calculus formation were observed only in the urinary bladder of male rats given the 0.3% bisacodyl diet. Proliferative lesions and increases of bromouracil deoxyriboside (BUdR) labeling indices were found only in the urinary bladder epithelium of rats with calculi, the severity of the former correlating with the calculus weight and being most marked in the dome areas, which are susceptible to physical stimulation. These findings indicate a close relationship between the development of proliferative lesions and the existence of calculi in the urinary bladder, and suggest that bisacodyl-induced proliferative lesions are not caused directly by bisacodyl per se but are secondary to calculus formation.
研究发现，在F344/DuCrj大鼠的膀胱中，膳食补充浓度范围为1%至0.3%的比沙可啶会诱发结石和上皮增殖性病变，包括移行细胞癌。为了阐明比沙可啶相关的膀胱结石与膀胱增殖性病变发展之间的关系，对雄性和雌性大鼠分别给予浓度为0.3%、0.1%和0.03%的比沙可啶饮食，持续32周。在整个实验期间，接受比沙可啶治疗的两性动物均出现腹泻。仅在给予0.3%比沙可啶饮食的雄性大鼠膀胱中观察到上皮增殖性病变和结石形成。仅在患有结石的大鼠膀胱上皮中发现增殖性病变和溴尿嘧啶脱氧核苷（BUdR）标记指数增加，前者的严重程度与结石重量相关，在易受物理刺激的穹窿区域最为明显。这些发现表明膀胱中增殖性病变的发展与结石的存在密切相关，并提示比沙可啶诱导的增殖性病变并非直接由比沙可啶本身引起，而是继发于结石形成。
