Rapid induction of dog urinary bladder cancer for the human bladder cancer model.

人类膀胱癌是一种从低分级-低分期到高分级-高分期的广谱疾病。然而，膀胱癌实验模型在多种致癌物的诱导下也仅限于一种类型的癌症。狗膀胱癌模型的优点是狗发展两种类型的膀胱癌和临床检查和治疗能够像人类一样执行。该模型的缺点是诱导膀胱癌需要较长的时间。在本实验中，我们尝试通过膀胱内灌注m -甲基-n -亚硝基脲（MNU）和口服n -丁基-n -（4-羟基丁基）亚硝胺（BBN）快速诱导狗膀胱癌。6只雌性Beagle犬在口服BBN 240mg/d后，每3周3次给予MNU 50mg/0.9NaCl 20ml， 2只犬单独给予MNU滴注。80周的冷杯活检显示发育不良，但未观察到CIS。169周膀胱镜下见结节状或无蒂乳头状肿瘤，为2级移行性癌，pT1b，结节性增生至粘膜下层。单用MNU治疗犬未见膀胱肿瘤。这些组织学结果表明这些肿瘤是由CIS病变发展而来的。该实验犬模型采用BBN和MNU联合治疗，密切观察CIS及其发展过程，有助于研究人类膀胱癌的自然史。

Human urinary bladder cancer is wide-spectrum disease ranging from low grade-low stage to high grade-high stage cancer. However, experimental bladder cancer model are restricted to have one type of cancer even induced by various carcinogens. The advantage of dog bladder cancer model is that the dog develop both types of bladder cancer and the clinical examination and treatment is able to perform like a human. The disadvantage of this model is long period needed to induce the bladder cancer. In this experiment, we tried a rapid induction of dog bladder cancer using intravesical instillation of M-metyl-N-nitrosourea(MNU) and oral administration of N-butyl-N-(4-hydroxybutyl) nitrosamine(BBN). 6 female Beagle dogs received MNU 50mg/0.9NaCl 20ml 3 times every 3 weeks followed oral administration of BBN 240mg/day and 2 dogs received MNU instillation alone. Cold cup biopsies at 80 weeks revealed dysplasia but no CIS was observed. At 169 weeks, nodular or non-peduncle papillary tumor were observed cystoscopically, Which were transitional carcinoma, grade 2, pT1b with nodular proliferation into the submucosal layer. Bladder tumor was not observed in the dogs treated MNU alone. These histological findings suggest that these tumor progressed from CIS lesions. This experimental dog model treated with BBN and MNU combined treatment seems to be useful in the study of the natural history of human urinary bladder cancer with close observation for CIS and its development.