Low susceptibility of Long-Evans Cinnamon rats to N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis and inhibitory effect of urinary copper
Y. Chone et al., Low susceptibility of Long-Evans Cinnamon rats to N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis and inhibitory effect of urinary copper, JPN J CANC, 91(1), 2000, pp. 16-24
We studied the susceptibilities to N-butyl-N-(4-hydroxybutyl)nitrosamine (B
BN)-induced urinary bladder carcinogenesis of male Long-Evans Cinnamon (LEC
), F344 and Long-Evans Agouti (LEA) rats. Male rats (n=21) were given 0.1%
BBN in their drinking water from week 6, 8 and 10 for one week, and killed
in week 56. The incidences of transitional cell tumors (papillomas plus car
cinomas) in BBN-treated LEC and F344 rats were 12% and 76%, respectively (P
<0.001, experiment 1), and those in LEC and LEA rats were 11% and 95%, resp
ectively (P<0.001, experiment 2). When male LEC and F344 rats were given 0.
1% BBN in their drinking water for 7 days, the intake of BBN and the urinar
y concentration of its active metabolite, N-butyl-N-(3-carboxypropyl)nitros
amine (BCPN), were higher in the LEC rats (P<0.01). The urinary pHs of untr
eated LEC and F344 rats were similar between week 6 and 30. The urinary cop
per 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 tim
es those in F344 rats. In a two-stage carcinogenesis study using F344 rats,
i.p. injections of cupric nitrilotriacetate increased urinary copper excre
tion, and inhibited BBN-induced bladder carcinogenesis. In a two-stage carc
inogenesis study using LEC rats, oral administration of D-penicillamine dec
reased urinary copper excretion, and increased BBN-induced bladder cancer,
although the difference was not significant. These data show that LEC rats
are resistant to bladder carcinogenesis and suggest that urinary copper has
a significant role in their resistance.