Induction of renal carcinoma in dog

本研究以N-乙基-N-羟乙基亚硝胺(EHEN)为引发剂，以β-环糊精(β-C)为促进剂，对犬肾化学致癌作用进行了研究。由于狗在接受β-C治疗后出现了肾毒性的迹象，正如在大鼠身上所报道的那样，狗似乎也可以作为肾病的模型。如果要将该模型应用于肾癌的研究，本研究建议β-C的最佳剂量方案为7天0.45g/kg治疗。在另一项初步研究中，我们检测了临床上用作肾癌标记物的各种参数，这些参数被用于EHEN诱发的肾癌大鼠的肾癌模型。本实验选用7只雌性Beagle犬，体重8.1~10.5 kg，平均9.2 kg。实验动物分为5组：1组(2只犬服用300 mg的EHEN并随后服用β-C)，2组(2只狗服用150 mg的EHEN并随后服用β-C)，3组(1只单独服用300 mg的EHEN)，4组(1只只服用150 mg的EHEN)和5组(1只只服用β-C)。口服伊亨14天为一疗程。所有动物都接受了肾脏超声检查和血液采样，以获得各种参数。从实验开始，这些检查每3个月进行一次。术后18个月(79周)，US显示各组犬肾脏均未见肿瘤形成。此外，包括Ep在内的任何参数都没有明显的升高，应继续用US和采血对这些动物进行进一步观察。

Present investigation was conducted to examine the chemical renal carcinogenesis using N-ethyl-N-hydroxyethylnitrosamine (EHEN) as a initiator and beta-cyclodextrin (beta-C) as a promoter in dogs.In one of preliminary studies, we examined nephrotoxicity of subcutaneous administration of beta-C in dogs. Because signs of nephrotoxicity represented were noted in dogs after beta-C treatment, as has been reported in rats, it seems likely that dogs also can serve as a model of nephrosis. If this model is to be applied to the study of renal carcinogenesis, this study suggested the optimum dosing regimen for beta-C to be 7-day 0.45g/kg treatment.In another preliminary study, we examined various parameters, which are clinically used as tumor markers of renal cell carcinoma, in renal tumor-bearing rats induced by EHEN. The results from this experiment suggested that erythropoietin (EP) was specially elevated in rats with renal tumor.In the present experiment, seven female Beagle dogs, weighing 8.1-10.5kg (mean : 9.2kg) were used. The animals were divided into five groups : Group 1 (2 dogs treated with 300mg of EHEN and with subsequent beta-C), Group 2 (2 dogs treated with 150mg of EHEN and with subsequent beta-C), Group 3 (1 dog treated with 300mg of EHEN alone), Group 4 (1 dog treated with 150mg of EHEN alone) and Group 5 (1 dog treated with beta-C alone). Duration of oral administration of EHEN was 14 days. All animals were followed with ultrasonography (US) of the kidneys and blood sampling for various parameters. Those examinations were performed every 3 months from the beginning of the experiment. On 18 months (79 weeks), US indicated no tumor formation in the dog kidneys in all groups. In addition, no significant elevations were noted in any parameters including EP.Further observations of those animals with US and blood sampling should be continued.