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

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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.