Urinary putrescine and plasma lactate dehydrogenase as markers of experimental adenocarcinoma growth

Abstract

The objective of this study was to assess, in a controlled experimental system, whether changes in urinary polyamine excretion reflect growth of a solid tumor, and whether such changes are dependent on the location of the tumor. A transplantable N-methyl-N′-nitro-N-nitrosoguanidine-induced adenocarcinoma (NG-W1) was grown intrahepatically or s.c. in male Wistar rats. Tumor size was measured at various time intervals and blood samples and 24-hr urines were collected. Analyses of 24-hr urines for their polyamine content, using a thin-layer chromatographic method for the separation of the dansylated polyamine derivatives, revealed a positive correlation between the 24-hr putrescine output and the increasing tumor burden. Notably, the 24-hr urine volume was found to parallel the increase in 24-hr putrescine excretion. The 24-hr urinary excretion of spermidine remained constant throughout tumor growth as did that of creatinine. Analyses of blood plasma for its lactate dehydrogenase activity, using a spectrophotometric technique, indicated no relationship between plasma lactate dehydrogenase activity and tumor burden, except at a large tumor mass. The increase in 24-hr urinary putrescine excretion in rats harboring an intrahepatic tumor preceded that which occurred in rats harboring an s.c. tumor. This time lapse was attributable to the fact that the tumor growth characteristics, including vascularization, differed between the two locations; intrahepatic tumors having more extensive growth and better vascularization than s.c. tumors. The fact that the urine putrescine excretion, particularly in a site such as the liver, is an early marker of tumor progression, indicates that this polyamine may be helpful in appraising relapse and recurrence of cancer.