It has been known that cancer patients excrete unusual amounts of the polyamine putrescine, spermidine, and spermine in their urine compared to normals. These return to normal levels on successful therapy. Most of the earlier investigation involved hydrolysis to obtain the free polyamines before determinations. Use of these determinations were confined to the monitoring of suspected cancer patients for tumor progression, regression and to evaluate the efficacy of a particular course of therapy in conjunction with other known diagnostic aids. This was because of a number of false positives and negatives. Serial determinations, use of ion exchange columns coupled with automatic instruments such as HPLC, post derivatization and fluorescent detection have removed all false positives leaving only one case of a false negative. Because putrescine and spermidine exist as acetyl derivatives in the urine of normal and cancer patients, and because urinary putrescine changes are more remarkable and occur much earlier than the other polyamines, monitoring acetylputrescine has potential as an early cancer marker. Accordingly, it is proposed to: a) induce tumor in Sprague-Dawley rats; b) collect twenty-four hour urine samples at well designated intervals; c) analyze, using HPLC, ion exchange column, post derivatization, and fluorescence detectors, the urine, blood and tissue samples for acetylpolyamines, and express the findings as normalized to creatinine; d) correlate if possible the acetylputrescine content to tumor incidence; e) confirm tumor presence through histopathological examination. Success of this project will lead to earlier detection in the population predisposed to cancer by serial examination of urine and will lead to earlier treatment of cancer than will otherwise be the case. This is particularly significant because the American Cancer Society estimates that of about one million who will have cancer, nearly half a million will die in 1986.
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