A histopathological mapping study of the urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in dogs.
Bladder tumors were induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in five Beagles and four mongrel dogs. The tumors were observed for long periods and the tumor progression was traced using histopathological mapping. The results indicated (1) that low-dose BBN over a long period induced multiple low-grade (G1-2) and low-stage (pTa-1) papillary tumors, resembling superficial bladder cancer in humans; (2) that high-dose BBN over a short period induced high-grade (G2-3) and high-stage (pT3b) nonpapillary tumors and carcinoma in situ (CIS) resembling invasive cancer and CIS in humans; (3) that beagle dogs required longer periods and higher total doses of BBN as compared with mongrel dogs; (4) that the tumors induced by low-dose BBN in beagles were observed without BBN as long as the animals lived, and neither increasing numbers of tumors nor malignant features such as deep infiltration and metastasis was observed; and (5) that low-dose BBN seems to induce mild dysplasia, which is followed by Brunn's nest-like proliferation in the lamina propria and nodular change, eventually leading to the development of papillary noninvasive transitional cell carcinoma (TCC); and that high-dose BBN seems to induce severe dysplasia which leads to CIS and nonpapillary invasive TCC. These results may contribute to clarifying the natural history of human bladder cancer.
Okajima
E
E
Department of Urology, Nara Medical University, Japan.
Ozono
S
S
Yoshida
K
K
Samma
S
S
Momose
H
H
Iwai
A
A
Uemura
H
H
Tabata
S
S
Tsumatani
K
K
Hirao
Y
Y
Tsunemi
K
K
D000818:Animals; D002085:Butylhydroxybutylnitrosamine; D002273:Carcinogens; D002291:Carcinoma, Papillary / Q000139:chemically induced* / Q000473:pathology*; D018450:Disease Progression; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D009361:Neoplasm Invasiveness / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000473:pathology*
D002273:Carcinogens; D002085:Butylhydroxybutylnitrosamine