URINARY-EXCRETION OF MODIFIED NUCLEOSIDES IN PATIENTS WITH MALIGNANT MESOTHELIOMA

Abstract

TRNA is the most complex biomacromolecule in both structure and function. The complexity of its structure is caused by a large variety of enzymes which add modifying groups to the 4 bases after the primary synthesis. The most abundant of these enzymes are the tRNA methylases, which add methyl groups at various positions in the macromolecule. these methylating enzymes were, without exception, aberrantly hyperactive in every malignant tumor examined. In turn, every malignant tumor contains a few tRNA that are different in structure from the tRNA in the normal tissue. Again, there is no exception. These are the 1st qualitatively different biochemical components of every malignant cell, not more or less but different tRNA. Cancer patients excrete in their urine elevated levels of certain methylated bases. From the structure of these bases and knowledge of their method of synthesis, most come from the breakdown of tRNA. Their elevation in the urine stems from an extraordinarily high rate of turnover of tRNA in tumor tissue. Highly sophisticated, sensitive methods of analysis were developed for the determination of the modified nucleosides in the urine of cancer patients. When related to the creatinine level of the urine, some of the modified nucleosides and products derived from them were elevated in a large variety of tumors. Perhaps more important, these elevated levels return to normal after effective chemotherapy. These markers may also be useful in monitoring the effectiveness of therapy. Initial studies on the detection of cancer in asbestos workers and possible premalignant conditions in workers with asbestosis are reported.