HINO Okio Cancer Research Institule, Dept.of Experimental Pathlogy, 実験病理部, 部長 (90127910)
HIRABAYASHI Shinichi Teikyo University, Dept.of Pediatric Surgery, 医学部・附属病院, 教授 (60173259)
TSUCHIDA Yoshiaki The University of Tokyo, Dept.of Pediatric Surgery, 医学部・附属病院, 教授 (80010164)
上井 義之 東京大学, 医学部・附属病院, 助手 (70177567)
|Budget Amount *help
¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1996 : ¥3,000,000 (Direct Cost : ¥3,000,000)
In the first stage of this study, we confirmed histopathologically that transplacental administration of a carcinogenic agent, N-ethyl-N-nitrosourea (ENU) to pregnant rats induced in their F1 generations various renal lesions, such as simple renal cysts, Wilms tumor precursor lesions (nephrogenic rests), renal cell carcinomas, and adenomas. It was also shown that ENU-treated F1 generations inevitably suffered from fatal CNS tumors.
In the second stage, we performed renal transplantation experiments. In an attempt to further promote ENU-induced renal carcinogenesis devoid of influence of fatal CNS tumor involvements, we removed the right kidneys of the 15 ENU-treated F1 rats, and transplanted them orthotopically to the healthy F1 rats. Out of 15 kidneys transplanted, 9 were successfully taken as donor kidneys. Following 2 to 5 month long observation period, the transplants were removed and submitted to histopathological analysis for the possible Wilms precursors and tumors perse. Macro-and microscopic studies revealed that the Wilms tumor precursor lesion was found in only one kidney, and marked atrophy of renal parenchyma was observed in 5 kidneys, presumably due to postoperative stenotic process formation at the anastomosed renal vessels. It seemed that further effort to improve technical skills in microscopic surgery is mandatory to obtain higher success rate in renal transplantation procedures.
Because of the low success rate obtained in renal transplantation, it was impossible to conduct molecular biological studies for Wilms tumor suppressor genes.