Gofrit Ofrer N, Birman Tatiana, Dinaburg Anna, Ayesh Suhail, Ohana Patricia, Hochberg Abraham
Department of Biological Chemistry, Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.
Urology. 2006 Jul;68(1):231-5. doi: 10.1016/j.urology.2006.03.022.
Carcinogen-induced bladder cancer in rodents is a key model for evaluation of novel therapies for bladder cancer because of its similarity to the clinical disease. The major drawback of the model is the difficulty in assessing tumor burden in living animals and at necropsy. The objective of this work was to present simple and accurate solutions for this problem.
Sixty female Wistar rats were given N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) at a concentration of 0.05% in the drinking water for 35 weeks. Periodic evaluation of tumorigenesis was done by ultrasonography of the anesthetized animals. The tumor burden was evaluated after killing the rats by weighing the bladder, digital measurement of the tumor dimensions, and histologic examination.
Focal urothelial hyperplasia was noted by the 5th BBN week, severe dysplasia by the 15th BBN week, and transitional cell carcinoma from the 20th week on. Carcinoma was seen on digital photographs taken from the 20th week on. Tumors as small as 1 mm could be easily measured. A poor correlation (R2 = 0.33) was found between bladder weight and the digital photographic measurements of small tumors (20th BBN week). However, when larger tumors were considered (30th BBN week), a good correlation was found (R2 = 0.81).
Tumor progress in the rat BBN model was accurately monitored by ultrasonography in living animals. Digital measurement of tumor dimensions provided a precise method for evaluation of tumor burden at necropsy.
由于致癌物诱导的啮齿动物膀胱癌与临床疾病相似，它是评估膀胱癌新疗法的关键模型。该模型的主要缺点是难以在活体动物和尸检时评估肿瘤负荷。这项工作的目的是为这个问题提供简单而准确的解决方案。
60只雌性Wistar大鼠饮用含0.05% N-丁基-N-(4-羟丁基)亚硝胺（BBN）的水35周。通过对麻醉动物进行超声检查定期评估肿瘤发生情况。在处死大鼠后，通过称量膀胱重量、数字测量肿瘤尺寸和组织学检查来评估肿瘤负荷。
在BBN处理第5周时发现局灶性尿路上皮增生，第15周时出现重度发育异常，从第20周开始出现移行细胞癌。从第20周开始在数码照片上可见癌。小至1毫米的肿瘤都能轻松测量。膀胱重量与小肿瘤（BBN处理第20周）的数码照片测量值之间相关性较差（R2 = 0.33）。然而，当考虑较大肿瘤（BBN处理第30周）时，发现相关性良好（R2 = 0.81）。
通过超声检查可在活体动物中准确监测大鼠BBN模型中的肿瘤进展。肿瘤尺寸的数字测量为尸检时评估肿瘤负荷提供了一种精确方法。
