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Induction of renal carcinoma in dog

犬肾癌的诱导

基本信息

批准号：
01570903
负责人：
OKAJIMA Eigoro
金额：
$ 1.34万
依托单位：
Nara Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1991
项目状态：
已结题

项目摘要

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.

本研究以N-乙基-N-羟乙基亚硝胺（EHEN）为引发剂，β-环糊精（beta-C）为促进剂，在犬体内研究化学性肾脏致癌作用。在一项初步研究中，我们研究了皮下注射beta-C对犬的肾毒性。由于在β-C处理后，在犬中观察到了肾毒性体征，正如在大鼠中报告的那样，因此犬似乎也可以作为肾病模型。如果将该模型应用于肾癌的研究，本研究建议β-C的最佳给药方案为0.45g/kg，连续7天。在另一项初步研究中，我们检测了EHEN诱发的肾肿瘤大鼠的各种参数，这些参数被临床用作肾癌的肿瘤标志物。本实验选用7只体重8.1-10.5kg（平均9.2kg）的Beagle犬，在肾肿瘤大鼠中，促红细胞生成素（EP）明显升高。将动物分为5组：第1组（2只犬接受300 mg EHEN治疗，随后接受β-C治疗）、第2组（2只犬接受150 mg EHEN治疗，随后接受β-C治疗）、第3组（1只犬仅接受300 mg EHEN治疗）、第4组（1只犬仅接受150 mg EHEN治疗）和第5组（1只犬仅接受β-C治疗）。口服EHEN的持续时间为14天。对所有动物进行肾脏超声检查（US），并采集血液样本以获得各种参数。这些检查从实验开始每3个月进行一次。18个月（79周）时，US显示所有组的犬肾脏均无肿瘤形成。此外，在包括EP在内的任何参数中均未观察到显著升高。应继续对这些动物进行US和血样采集的进一步观察。