The Induction of Bladder Tumors in F344 Rats by Intravesicular Administration of Some Nitrosamines

Three nitrosamines, metabolically related and formed in vivo from the bladder carcinogen nitrosomethyl‐n‐octylamine, were administered to groups of 12 female F344 rats by intraurethral instillation twice a week for 30 weeks. All three compounds induced tumors in the urinary bladder. Nitrosomethyl‐2‐oxopropylamine at 10 mg/ml was the most potent, causing death of half of the animals with tumors at 43 weeks, following a total dose of 1.0 mmol; most of the rats also had tumors of the nasal mucosa, and there were some tumors of the kidney and kidney pelvis. Nitrosomethyl‐2‐hydroxypropylamine at 10 mg/ml (total dose 1.0 mmol) was much less effective, the median week of death being 83 weeks. In addition to bladder tumors, this group had tumors of the nasal mucosa, esophagus, and kidney. Nitrosomethyl‐3‐carboxypropylamine at 75 mg/ml and a total dose of 6.2 mmol per rat induced a high incidence of bladder tumors and tumors of the kidney pelvis, but not tumors of the nasal mucosa; the median week of death for this group was 55 weeks. It is concluded that nitrosomethyl‐n‐alkylamines that induce bladder tumors by oral administration to rats are metabolized to nitrosomethyl‐3‐carboxypropylamine, which is excreted in the urine and further metabolized to nitrosomethyl‐2‐oxopropylamine, the proximate bladder carcinogen.