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，β -环糊精（β -c）为启动子，研究狗的化学肾癌发生。在一项初步研究中，我们检查了狗皮下给药β - c的肾毒性。因为在β - c治疗后，狗的肾毒性症状被注意到，正如在大鼠中报道的那样，狗似乎也可以作为肾病的模型。如果将该模型应用于肾癌发生的研究，本研究建议β - c的最佳给药方案为0.45g/kg治疗7天。在另一项初步研究中，我们在EHEN诱导的肾荷瘤大鼠中检测了临床用作肾细胞癌肿瘤标志物的各种参数。本实验结果提示肾肿瘤大鼠红细胞生成素（EP）明显升高。本实验选用7只雌性Beagle犬，体重8.1-10.5kg（平均9.2kg）。将实验动物分为5组：1组（2只EHEN 300mg并加β - c）、2组（2只EHEN 150mg并加β - c）、3组（1只EHEN单独加300mg）、4组（1只EHEN单独加150mg）和5组（1只EHEN单独加β - c）。口服EHEN的疗程为14 d。对所有动物进行肾脏超声检查，并对各种参数进行血液采样。实验开始后每3个月进行一次检查。在第18个月（79周）时，US显示各组狗肾脏未形成肿瘤。此外，包括EP在内的任何参数均未发现明显升高。应继续对这些动物进行进一步观察，并进行血液取样。

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.