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Study on the bladder cancer susceptibility gene and the inhibitory factor of bladder cancer in rats

大鼠膀胱癌易感基因及膀胱癌抑制因子的研究

基本信息

批准号：
10670208
负责人：
IZUMI Keisuke
金额：
$ 1.86万
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：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670208/
关键词：
LEC rat bladder carcinogenesis susceptibility gene linkage analysis copper 低感受性

项目摘要

1) We found that the LEC rat is resistant to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced urinary bladder carcinogenesis. When male LEC and F344 rats were given 0.1% BBN in their drinking water for 7 days, the intake of BBN and urinary concentration of its active metabolite, N-butyl-N-(3-carboxypropyl)nitrosamine, were higher in the LEC rats (P<0.01). The urinary pHS of untreated LEC and F344 rats were similar between week 6 and 30. The urinary copper concentration was lower in LEC rats before jaundice than in F344 rats, but its concentrations in 28- and 50-week-old LEC rats were 1.7 and 2.3 times those in F344 rats. In a two-stage carcinogenesis study using F344 rats, i.p. injections of cupric nitrilotriacetate increased urinary copper excretion, and inhibited BBN-induced bladder carcinogenesis. In a two-stage carcinogenesis study using LEC rats, oral administration of D-penicillamine decreased urinary copper excretion, and increased BBN-induced bladder cancer, although the difference was not significant. These data suggest that urinary copper has an inhibitory effect on bladder carcinogenesis.2) We tried to identify possible quantitative trait loci responsible for low susceptibility to BBN-induced bladder carcinogenesis in LEC rats using (F344 x LEC)F2 rats, but we could not find any loci yet. There is no clear evidence that Atp7b gene is related to its low susceptibility.

1)我们发现LEC大鼠对N-丁基-N-（4-羟丁基）亚硝胺（BBN）诱发的膀胱癌有抵抗作用。雄性LEC和F344大鼠连续7天饮用0.1%BBN，LEC大鼠BBN摄入量和其活性代谢物N-丁基-N-（3-羧丙基）亚硝胺尿浓度均显著高于对照组（P<0.01）。未处理LEC和F344大鼠的尿pHS在第6周和第30周之间相似。黄疸前LEC大鼠尿铜浓度低于F344大鼠，但28和50周龄LEC大鼠尿铜浓度分别是F344大鼠的1.7和2.3倍。在使用F344大鼠的两阶段致癌研究中，腹腔注射氨三乙酸铜增加尿铜排泄，并抑制BBN诱导的膀胱癌发生。在一项使用LEC大鼠的两阶段致癌研究中，口服D-青霉胺可降低尿铜排泄，并增加BBN诱导的膀胱癌，尽管差异不显著。这些数据表明，尿铜对膀胱癌的发生具有抑制作用。2）我们试图用（F344 x LEC）F2大鼠鉴定LEC大鼠对BBN诱导的膀胱癌发生的低易感性的可能的数量性状位点，但我们还没有找到任何位点。Atp 7 b基因与其低易感性的关系尚不明确。