Influence of total dose and dose schedule on induction of urinary bladder cancer in the mouse by N-butyl-N-(4-hydroxybutyl)nitrosamine.
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.
D000818:Animals; D002085:Butylhydroxybutylnitrosamine / Q000494:pharmacology*; D002273:Carcinogens; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced; D009602:Nitrosamines / Q000494:pharmacology*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced*
D002273:Carcinogens; D009602:Nitrosamines; D002085:Butylhydroxybutylnitrosamine