Steele G, Crissey M, Gittes R, Harte P, Wilson R, Corson J
Cancer. 1981 May 1;47(9):2218-21. doi: 10.1002/1097-0142(19810501)47:9<2218::aid-cncr2820470918>3.0.co;2-s.
An animal model of organ-specific chemical carcinogenesis has been used to study environmental effects on the incidence of human colorectal adenocarcinoma. Wistar/Furth weanling rats underwent connection of their urinary and fecal streams (ureterosigmoidostomy), connection of their urinary and fecal streams with proximal fecal diversion (rectal bladder), or sham operations. Age-matched, unoperated control and operated animals then received either no carcinogen, 1,2-dimethylhydrazine (DMH) 20 mg/kg body weight, s.c. once weekly for 16 weeks, N-[4-(5-nitro-2-furyl)-2-thiazolylformamide (FANFT) 0.2% of the feed for 16 weeks, or DMH + FANFT concurrently. Thirty-three weeks after carcinogen exposure, surviving animals were killed and examined for bowel and urinary bladder tumors. The incidence of adenocarcinoma of the colon adjacent to the junction between bladder and bowel was significantly higher in animals after ureterosigmoidostomy compared with animals whose fecal stream had been proximally diverted (14/22 vs. 0/34, P less than 0.001). This effect was not dependent upon chemical carcinogen exposure. Nonexposed animals still developed a significantly higher incidence of colon adenocarcinomas adjacent to their bladder-bowel junctions as compared with animals with proximal fecal diversion (5/8 vs. 0/13, P less than 0.01). In unoperated or sham operated animals, adenocarcinomas of the bowel occurred in 33% of DMH-treated animals and transitional cell carcinomas of the urinary bladder in 33% of the FANFT-treated animals. After concurrent exposure to both carcinogens, no increased incidence of bladder tumors was noted when compared with FANFT treatment alone. However, the number of animals with one or more adenocarcinomas of the bowel (22/30 vs. 17/50, P less than 0.001), the mean number of tumors per animal (2.1 +/- 0.2 vs. 1.1 +/- 0.1, P less than 0.01), and the invasiveness of the tumors were all increased after DMH + FANFT as compared with DMH exposure alone. The carcinogenic potential of direct bladder to bowel connection with intact fecal and urinary streams, and the potentiation by FANFT of DMH-induced colon carcinogenesis may have implications in the genesis of human colorectal cancer.
一种器官特异性化学致癌动物模型已被用于研究环境因素对人类结肠腺癌发病率的影响。将Wistar/Furth断乳大鼠进行尿流和粪流连接（输尿管乙状结肠吻合术）、尿流和粪流连接并近端粪便改道（直肠膀胱术）或假手术。然后，将年龄匹配的未手术对照动物和手术动物分为未接受致癌物组、皮下注射1,2 - 二甲基肼（DMH）20 mg/kg体重、每周一次共16周组、饲料中含0.2% N - [4 - （5 - 硝基 - 2 - 呋喃基） - 2 - 噻唑基]甲酰胺（FANFT）共16周组，或同时给予DMH + FANFT组。致癌物暴露33周后，处死存活动物并检查肠道和膀胱肿瘤。与粪流近端改道的动物相比，输尿管乙状结肠吻合术后动物膀胱与肠道交界处相邻结肠的腺癌发病率显著更高（14/22 vs. 0/34，P < 0.001）。这种效应不依赖于化学致癌物暴露。与粪流近端改道的动物相比，未暴露动物在其膀胱 - 肠道交界处相邻结肠的腺癌发病率仍显著更高（5/8 vs. 0/13，P < 0.01）。在未手术或假手术动物中，33%接受DMH治疗的动物发生肠道腺癌，33%接受FANFT治疗的动物发生膀胱移行细胞癌。与单独给予FANFT相比，同时暴露于两种致癌物后，未观察到膀胱肿瘤发病率增加。然而，与单独给予DMH相比，DMH + FANFT组出现一个或多个肠道腺癌的动物数量（22/30 vs. 17/50，P < 0.001）、每只动物的平均肿瘤数量（2.1 ± 0.2 vs. 1.1 ± 0.1，P < 0.01）以及肿瘤的侵袭性均增加。完整尿流和粪流情况下膀胱与肠道直接连接的致癌潜力以及FANFT对DMH诱导的结肠癌发生的增强作用可能对人类结直肠癌的发生具有启示意义。
