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

1)我们发现LEC大鼠对N-丁基-N-(4-羟基丁基)亚硝胺(BBN)诱导的膀胱癌具有抵抗力。雄性LEC和F344大鼠饮用0.1%BBN 7d后，BBN的摄入量及其活性代谢物N-丁基-N-(3-羧丙基)亚硝胺的尿量均高于LEC大鼠(P&lt；0.01)。未处理的LEC和F344大鼠在第6~30周的尿PHS相似。黄疸前LEC大鼠尿铜浓度低于F344大鼠，但28周龄和50周龄LEC大鼠尿铜浓度分别是F344大鼠的1.7和2.3倍。在一项使用F344大鼠的两阶段致癌研究中，I.P.注射硝酸三乙酸铜可增加尿铜排泄，抑制BBN诱导的膀胱癌的发生。在使用LEC大鼠的两阶段致癌研究中，口服D-青霉胺减少了尿铜排泄，增加了BBN诱发的膀胱癌，尽管差异不显著。2)我们利用(F344×LEC)F2大鼠对BBN诱导的LEC大鼠膀胱癌易感性低的可能的数量性状基因座进行了筛选，但没有发现任何可能的基因座。目前尚无明确证据表明ATP7B基因与其低易感性有关。

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.