Differences Among Three Sister Strains of NON/Shi Mice in Sensitivity to Urinary Tract Carcinogenesis by N-Butyl-N-(4-hydroxybutyl)nitrosamine

Abstract

In this study we examined the susceptibility of three sister inbred strains of mice, NON/Shi, CTS/Shi, and NOD/Shi to the urinary bladder carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in an attempt to optimize our model for tumor induction and spontaneous metastasis. The animals were given BBN at a dose of 0.05% in drinking water for 8 weeks and then maintained without further treatment until week 24 when the renal pelvis and urinary bladder were examined microscopically. The incidences of renal pelvic and urinary bladder carcinomas in NON/Shi, CTS/Shi, and NOD/Shi were 13/25 (52%) and 11/25 (44%), 3/19 (16%) and 12/19 (63%), and 0/24 (0%) and 1/24 (4%), respectively. Metastasis to lungs was only observed in renal pelvic carcinoma-bearing NON/Shi mice at an incidence of 77%. Invasion of the prostate and/or intraperitoneal dissemination were observed in urinary bladder carcinoma-bearing NON/Shi and CTS/Shi mice at incidences of 18% and 25%, respectively. BBN intake was highest in NON/Shi mice but urinary concentrations of the carcinogen and its ω-oxidative metabolite, N-butyl-N-(3-carboxypropyl) nitrosamine did not differ among the three strains. These results indicate that NON/Shi is the most sensitive of the three strains to carcinogenic effects of BBN on the urinary tract, particularly renal pelvis, and therefore the most suitable for our spontaneous metastasis model.