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Urinary Excretion of N¹-Acetylspermidine and Other Acetylated and Free Polyamines in the 1,2-Dimethylhydrazine Model of Experimental Rat Colon Cancer¹

Departments of Medicine, The University of Chicago Hospitals and Clinics, Pritzker School of Medicine, University of Chicago, Chicago, Illinois 60637

1,2-Dimethylhydrazine (DMH) is a potent procarcinogen with selectivity for the colon. Recently, it has been demonstrated that levels of N¹-acetylspermidine were elevated 2–3-fold in colonic tumors induced by this agent compared to control tissues. To determine whether alterations in the urinary levels of this acetylated polyamine or other polyamines were useful biochemical markers for colon cancer in this experimental model, rats were given s.c. injections of DMH (20 mg/kg body weight/week) or diluent for 26 weeks. One week after the last injection, control and DMH-treated animals were placed in separate metabolic cages and their urine was collected for 24 h. The urinary levels (expressed as nmol/mg creatinine) of putrescine, spermidine, spermine, N¹-acetylspermidine, and N⁸-acetylspermidine were then analyzed by high-performance liquid chromatography. Animals from each group were then sacrificed and their colons were examined for tumors.

The results of these studies demonstrated that the urinary level of N¹-acetylspermidine was an excellent biochemical marker for colonic tumors induced by DMH. At 18.3 nmol/mg creatinine, N¹-acetylspermidine was 100% sensitive and specific for colon cancer. Moreover, urinary levels of N¹-acetylspermidine were better for this purpose than the N¹-acetylspermidine/N⁸-acetylspermidine molar ratio, a marker previously suggested to be more specific for certain cancers than free polyamines.

¹ These investigations were supported by USPHS Grants CA 36745 and CA 08288 awarded by the National Cancer Institute, Department of Health and Human Services.

² Recipient of a Merit Award from the National Cancer Institute/NIH. To whom requests for reprints should be addressed, at Department of Medicine, The University of Chicago Hospitals and Clinics, Box 400, 5841 S. Maryland Avenue, Chicago, IL 60637.

Received 3/ 7/89. Revised 5/30/89. Accepted 6/ 8/89.