Arai M, Cohen S M, Jacobs J B, Friedell G H
J Natl Cancer Inst. 1979 Apr;62(4):1013-6.
Because of the utility of the N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) rat model in the study of bladder cancer, the effect of dose on FANFT-induced bladder carcinogenesis was evaluated. Weaning male F344 rats were given FANFT in the diet at doses of 0.1, 0.05, 0.01, 0.005, 0.001, and 0.0005% for 30 weeks and then a control diet for 22 weeks. A control group received only the control diet throughout the experiment. Papillary tumors were present at the higher doses, hyperplasia of various degrees of severly was present at the intermediate doses, and minimal hyperplasia was observed in 4 of 16 rats at the 0.005% dose; no mucosal abnormalities were observed at the two lower doses or in the control group. Bladder epithelium from selected animals was also examined by scanning electron microscopy (SEM) after 10 weeks and again at the end of the experiment. Hyperplastic mucosa with pleomorphic microvilli similar to that previously demonstrated for 0.2% FANFT was observed at 10 weeks in rats fed 0.1% FANFT. Hyperplastic mucosa with pleomorphic microvilli was also observed at 52 weeks in rats fed 0.1% and 0.05% FANFT. Hyperplastic mucosa without pleomorphic microvilli was observed in rats fed 0.01 and 0.005% FANFT. The bladder appeared normal by light microscopy and SEM at the two lower doses and in the control group at both the 10- and 52-week intervals. A dose relationship was thus demonstrated for FANFT-induced bladder carcinogenesis in male F344 rats, and more severe surface changes were observed by SEM as the dose increased.
由于N-[4-(5-硝基-2-呋喃基)-2-噻唑基]甲酰胺（FANFT）大鼠模型在膀胱癌研究中的实用性，评估了剂量对FANFT诱导膀胱癌发生的影响。将断乳雄性F344大鼠在饮食中给予0.1%、0.05%、0.01%、0.005%、0.001%和0.0005%剂量的FANFT，持续30周，然后给予对照饮食22周。对照组在整个实验过程中仅接受对照饮食。高剂量组出现乳头状瘤，中等剂量组出现不同程度的重度增生，0.005%剂量组16只大鼠中有4只出现轻度增生；两个低剂量组和对照组未观察到黏膜异常。在实验10周后及实验结束时，还通过扫描电子显微镜（SEM）对选定动物的膀胱上皮进行了检查。在喂食0.1% FANFT的大鼠中，在10周时观察到具有多形性微绒毛的增生性黏膜，与先前在0.2% FANFT中观察到的相似。在喂食0.1%和0.05% FANFT的大鼠中，在52周时也观察到具有多形性微绒毛的增生性黏膜。在喂食0.01%和0.005% FANFT的大鼠中观察到没有多形性微绒毛的增生性黏膜。在两个低剂量组以及10周和52周时的对照组中，膀胱通过光学显微镜和SEM观察均正常。因此，在雄性F344大鼠中证明了FANFT诱导膀胱癌发生的剂量关系，并且随着剂量增加，通过SEM观察到更严重的表面变化。
