Transfer RNA (tRNA) is a complex biomacromolecule containing a large number of modified bases. The modifications include methylation by several specific enzymes. These are hyperactive in malignant tumor tissue, which therefore contains tRNA that are different in structure form those present in normal tissue; they also have a high turnover rate. It is known that patients with cancer excrete in their urine elevated levels of such modified nucleosides (tumore markers). We have found abnormal levels of modified nucleosides in patients with asbestos related malignant mesothelioma, and we have shown in a feasibility study of individuals selected from the proposed study population but without clinical evidence of cancer tha asbestos insulation workers, with a history of long term exposure to asbestos and thus at high neoplastic risk, altered nucleoside excretion with appreciable prevalence. In the proposed investigation we will measure levels of modified nucleosides in the urine of 1,000 asbestos insulation workers with a history of 30 years or more from first onset of exposure. We will investigate whether the urinary excretion profile of nucleosides may be predictive of subsequent malignant disease One objective of the proposed study is therefore to investigate the usefulness of modified nucleoside levels in identifying individuals at high neoplastic risk. Extensive clinical and laboratory information is available on the proposed study population. The nucleoside pattern will be characterized for the entire population, and a matrix of intercorrelations between nucleosides and pertinent medical and laboratory information will be generated. Intra group differences will be evaluated for each nucleoside with respect to classification variables reflecting health affects of asbestos associated disease. The principal analysis of the proposed investigation will include prospective surveillance of all examined in terms of their mortality experience between 1984 and 1986. For this purpose we have developed a mechanism by which we will be made aware of the death of any individual in the study population. We will then study the association between the initial nucleoside excretion pattern and the mortality experience. Such information will provide important information about the significance of nucleoside levels and their capacity to serve as predictive markers for future malignant disease. Clarification of this may have important implications for prediction of occupational cancer.
