Dose-response relationships in the induction of
urinary bladder cancer in male C57BL/6 x DBA/2-F1 (BDF) mice by intragastric instillation of
N-butyl-N-(4-hydroxybutyl)nitrosamine (
OH-BBN) were studied. Administration of a total dose of 0 to 80 mg
OH-BBN in 10 weekly fractions to groups of 25 mice resulted in a linear increase in
carcinoma incidence with dose.
OH-BBN administration schedule had a significant effect on
cancer incidence: administration of a total dose of 30, 20, or 15 mg
OH-BBN in 20 weekly fractions was more effective in
cancer induction than was the same total dose given in 5 fractions.
A 10 dose administration schedule was of intermediate efficacy. The data obtained indicate that
OH-BBN induces urinary bladder
cancers in BDF mice in a dose-related manner, with high target organ-specificity, little toxicity, and short
tumor latency; induced
tumors are primarily
transitional cell carcinomas which morphologically resemble their human counterpart. Administration of
OH-BBN mice provides a useful model for the experimental study of
urinary bladder cancer.