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Major Urinary Metabolites in Hamsters and Rats Treated with N-Nitroso(2-hydroxypropyl)(2-oxopropyl)amine¹

Departments of Pathology, Molecular Biology, and the Cancer Center, Northwestern University Medical School, Chicago, Illinois 60611

Rats and hamsters were administered a single dose of N-[1-¹⁴C]nitroso(2-hydroxypropyl)(2-oxopropyl)amine (HPOP), and their urinary metabolites were examined at various time intervals. In both species, urinary excretion of radiolabeled metabolites reached a plateau at 6 h following injection. At this time, 35 and 28% of the total dose was found in the urine of rats and hamsters, respectively. Separation by liquid chromatography and subsequent characterization by nuclear magnetic resonance, gas chromatography-mass spectroscopy, and infrared showed that the major metabolites in rat urine were HPOP, N-nitrosobis(2-hydroxypropyl)amine (BHP), and their glucuronic acid conjugates. The conjugates accounted for 30 and 9%, while free HPOP and BHP accounted for 42 and 16% of the total metabolites, respectively. Hamster urine, on the other hand, contained free HPOP, BHP, their glucuronic acid conjugates, and a sulfate ester of HPOP not found in rat urine. Six h following administration of HPOP, hamster urine contained BHP, BHP glucuronide, HPOP, HPOP glucuronide, and HPOP sulfate ester at levels of 35, 9, 16, 9, and 14%, respectively. These data suggest that hamsters reduce HPOP to BHP more efficiently than rats, while rats are more effective in forming their glucuronic acid conjugates. Hamsters differ significantly from rats in their capacity to form and excrete the sulfate ester of HPOP.

¹ This work was supported in part by the Edith Patterson and Marie A. Fleming Cancer Research Funds, Northwestern University, and by Grants CA 34051 and CA 16954.

Received 1/23/85. Revised 4/24/85. Accepted 4/30/85.