Study of the Long-Evans Cinnamon (LEC) rat for a model of human renal carcinogenesis

Long-Evans Cinnamon (LEC) 大鼠作为人肾癌模型的研究

• 批准号: 07670250
• 负责人: IZUMI Keisuke
• 金额: $ 1.28万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670250/
• 关键词: LEC rat; spontaneous renal cell tumor; copper; Tsc2 gene; oxidative DNA damage; Loss of heterozygosity; VHL gene; Tso2遺伝子; 自然発生腎癌; 前がん病変

1. The role of copper and iron on the development of spontaneous renal cell tumors in Long-Evans Cinnamon (LEC) rats was investigated. Copper content in the kidneys of LEC rats in weeks 16-20 when necrotizing hepatitis occurred was 24 times higher than that in F344 rats. Then copper content decreased until 40 weeks, but it was always higher than that in F344 rats. Iron content in the kidney of LEC rats also peaked in weeks 16-20, but it was lower than that in F344 rats after 62 weeks old. Copper staining of the kidney in LEC rats showed positive staining in proximal tubules of the cortex and the outer stripe of the medulla. Long-term treatment of LEC rats with D-penicillamine, a copper-chelating agent, inhibited the development of karyomegaly and BrdU-positive dysplastic tubules. These results suggest that the copper-mediated oxidative DNA damage play an important role in the development of the spontaneous renal cell tumors in LEC rats.2. The role of VHL and Tsc2 genes on the development of renal cell tumors in LEC and F344 rats was investigated by PCR-SSCP.We could not find any mutation in VHL gene. However, we found the Tsc2 gene mutation in the renal cell tumors induced by DEN and EHEN,but not in spontaneous tumors. Loss of heterozygousity on chromosome 10 was found in one of eight (F344xLEC) F1 rats.

1. 研究了铜和铁在龙氏肉桂（Long-Evans Cinnamon， LEC）大鼠自发性肾细胞肿瘤发生中的作用。16-20周发生坏死性肝炎时，LEC大鼠肾脏铜含量比F344大鼠高24倍。铜含量下降至40周，但始终高于F344大鼠。LEC大鼠肾脏铁含量也在16-20周达到峰值，但在62周后低于F344大鼠。肾铜染色显示肾皮质近端小管和髓质外条纹呈阳性。长期用d -青霉胺（一种铜螯合剂）治疗LEC大鼠，可抑制核肥大和brdu阳性发育不良小管的发展。提示铜介导的DNA氧化损伤在LEC大鼠自发性肾细胞瘤的发生发展中起重要作用。采用PCR-SSCP方法研究VHL和Tsc2基因在LEC和F344大鼠肾细胞肿瘤发生中的作用。在VHL基因中未发现任何突变。然而，我们发现Tsc2基因在DEN和EHEN诱导的肾细胞肿瘤中发生突变，而在自发性肿瘤中没有发生突变。8只（f344 × lec） F1大鼠中有1只发现10号染色体杂合性缺失。

项目成果

Chai, J.et al: "Development of functional rat-derived T cells in SCID mice engrafted with the fetal thymus of LEC rats which are defective in CD4+ T cells." Microbiol.Immunol.40. 659-664 (1996)

Chai, J. 等人：“在移植有 CD4 T 细胞缺陷的 LEC 大鼠胎儿胸腺的 SCID 小鼠中开发功能性大鼠来源 T 细胞。”

Chai,J.: "Development of functional rat-derived T cells in SCID mice engrafted with the fetal thymus of LEC rats which are defective in CD4+ T cells." Microbiol.Immunol.40. 659-664 (1996)

Chai, J.：“在移植有 CD4 T 细胞缺陷的 LEC 大鼠胎儿胸腺的 SCID 小鼠中开发功能性大鼠来源 T 细胞。”

Muramatsu,Y.: "The rat homologue of the Wilson's disease gene was partially deleted at the 3'end of its protein-coding region in Long-Evans Cinnamon rats." Res.Comm.Mol.Pathol.Pharmacol.89. 421-424 (1995)

Muramatsu,Y.：“在 Long-Evans Cinnamon 大鼠中，威尔逊氏病基因的大鼠同源物在其蛋白质编码区的 3 端被部分删除。”

Muramatsu, Y.et al: "The rat homologue of the Wilson's disease gene was partially deleted at the 3'end of its protein-coding region in Long-Evans Cinnamon rats" Res.Comm.Mol.Pathol.Pharmacol.89. 421-424 (1995)

Muramatsu, Y.等人：“在 Long-Evans Cinnamon 大鼠中，威尔逊氏病基因的大鼠同源物在其蛋白质编码区的 3 端被部分删除”Res.Comm.Mol.Pathol.Pharmacol.89。

Muramatsu,Y.: "The rat homologue of the Wilson's disease gene was partially deleted at the 3' end of its protein-coding region in Long-Evans Cinnamon rats." Res.Comm.Mol.Pathol.Pharmacol.89. 421-424 (1995)

Muramatsu,Y.：“在 Long-Evans Cinnamon 大鼠中，威尔逊氏病基因的大鼠同源物在其蛋白质编码区的 3 端被部分删除。”