Comparison of Urinary Modified Nucleosides and Bases in Rats with Hepatomas and Nephroblastomas

Abstract

It has been known for more than 20 years that patients with cancer excrete greater than normal amounts of purine and pyrimidine derivatives in their urines (Adams et al. 1960; Park et al. 1962). The unmodified purine derivatives, adenine and guanine, are normally metabolized to uric acid, but in some instances they are not metabolized further and may be excreted or recycled into nucleic acids. The unmodified pyrimidine derivatives, cytosine and uracil, are usually degraded and excreted as ammonia and urea, but recycling and excretion may occur. It was not until the pioneering studies by Borek and his students on tRNA methyltransferases (Fleissner and Borek 1963) that the methylated nucleosides in the urine were shown to be derived from tRNA (Mandel et al. 1966). More recently, using more sensitive techniques, several groups of investigators have reported increased levels of modified nucleosides in urines from patients with cancer (Hogan et al. 1970; Waalkes et al. 1973; Mrochek et al. 1974; Senftleber et al. 1976; Davis et al. 1977; Gehrke et al. 1978; Speer et al. 1979; Hartwick et al. 1980). The increased levels of most modified nucleosides and bases in urine of hosts with neoplasms have been attributed to an increased rate of turnover of tRNA in cancer tissue (Borek et al. 1977). The evidence to date suggests that modified nucleosides or bases are not metabolized further and are quantitatively excreted into the urine (Weissman et al. 1962; Dlugajczyk and Eiler 1966). More than 20 modified nucleosides have been isolated from human urine (Chedda 1975).

The authors are indebted to Mr. Jeffrey Turner for excellent technical assistance and to the American Cancer Society for supporting this work with the Herbert P. Clauberg Memorial Grant for Cancer Research