Low susceptibility of Long-Evans Cinnamon rats to N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder carcinogenesis and inhibitory effect of urinary copper.
We studied the susceptibilities to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-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 carcinomas) 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%, respectively (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 urinary concentration of its active metabolite, N-butyl-N-(3-carboxypropyl)nitrosamine (BCPN), 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 show that LEC rats are resistant to bladder carcinogenesis and suggest that urinary copper has a significant role in their resistance.
Chone
Y
Y
Second Department of Pathology, The University of Tokushima School of Medicine.
Kinouchi
T
T
Yamada
T
T
Suzuki
Y
Y
Kitaura
K
K
Jiao
Z
Z
Minami
T
T
Bando
Y
Y
Uehara
H
H
Mochizuki
M
M
Ohnishi
Y
Y
Izumi
K
K
D000367:Age Factors; D000818:Animals; D002085:Butylhydroxybutylnitrosamine / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000652:urine*; D019327:Copper Sulfate / Q000494:pharmacology; D004198:Disease Susceptibility; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000652:urine; D008297:Male; D008668:Metallothionein / Q000378:metabolism; D010396:Penicillamine / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D020332:Rats, Inbred LEC; D020318:Rats, Long-Evans; D013045:Species Specificity; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D014556:Urine / Q000737:chemistry; D015032:Zinc / Q000652:urine
D002273:Carcinogens; D002614:Chelating Agents; D002085:Butylhydroxybutylnitrosamine; D003300:Copper; D008668:Metallothionein; D007501:Iron; D010396:Penicillamine; D015032:Zinc; D019327:Copper Sulfate