Local and systemic carcinogenic effects of alkylating carcinogens in rats treated by intravesicular administration

Several nitrosamines and an azoxyalkane have been administered intravesically to groups of 12 female F344 rats, twice a week for 20 or 30 weeks. Many of the nitrosamines were as efficacious in giving rise to the same tumors of internal organs as when similar doses were administered orally, showing that absorption from the bladder was as rapid as from other sites. The tumors produced included lung and kidney tumors by nitrosodimethylamine, colon and Zymbal gland tumors by azoxymethane, liver tumors by methylnitrosoethylamine (but not by nitrosodimethylamine), liver and esophagus tumors by nitrosodiethylamine, liver and lung tumors by methylnitrosamino-3-pyridylbutanone, liver tumors by nitrosomorpholine, and tumors of the esophagus by methylnitroso-n-butylamine, 2,6-dimethyl-nitrosomorpholine and methylnitrosamino-N,N-dimethylethylamine. Bladder tumors were induced by intravesicular administration of only low doses of nitrosobis-(2-oxopropyl)amine and to a lesser extent by methylnitroso-n-hexylamine and nitroso-(2-hydroxypropyl)(2-oxopropyl)amine, which all induced tumors systemically in addition. The bladder mucosa seemed to lack enzymes necessary to activate most nitrosamines to locally acting proximate carcinogens, but was quite transparent to the passage of carcinogenic nitrosamines present in the urine into the body to induce tumors in distant organs.