Production of N¹-acetyl spermidine by renal cell tumors

In the RPMI mouse renal cell tumor, N¹-acetylspermidine (N¹AS) was found to be constant and major component (18 to 25%) of the polyamine pool. Early i.m. growth induced urinary N¹AS excretions up to tenfold normal, equivalent to a daily turnover of the entire tumor polyamine pool. N¹AS excretion was correspondingly lower during more limited s.c. tumor growth. In nine other mouse tumors, N¹AS pools were low or negligible, and correspondingly urinary N¹AS or N⁸AS increased only in advanced growth, and less significantly. Urinary N¹AS was elevated likewise in immature untumored mice. Thus, the enriched N¹AS pool of the renal cell tumor was separately distinguishable as a direct source of elevation of urinary N¹AS. N¹AS was selectively abolished from the renal cell tumor by prolonged BCNU treatment, but was not rapidly depleted by the polyamine inhibitor DFMO. In cell culture, the RPMI renal cell tumor contained unusually high uninduced levels of sperm(id)ine N¹-acetyltransferase, a potential source of N¹AS. N¹AS pools were also significantly elevated in human renal cell tumors.