Transfer RNA breakdown products in the urine of asbestos workers

Patients with malignant mesothelioma, a neoplasia strongly associated with previous asbestos exposure, excrete in the urine high levels of modified purines, pyrimidines, and their ribosides, breakdown products of transfer RNA. The urinary excretion levels of modified nucleosides were measured in 47 male insulation workers with long term exposure to asbestos and, therefore, at high neoplastic risk. The nucleoside levels of 44 male control subjects were used for comparison. Asbestos-related radiographic changes were found in 70% of the exposed individuals. An increasing severity of radiographic alterations was associated with a greater frequency of elevated nucleoside clusters, especially in m'A, m'I, m'G, and m2(2)G. Duration since onset of exposure was directly related to pseudouridine, m'I, and m2(2)G. Though cigarette smoking contributes to the development of asbestos-related lung cancer, data are presented that support the hypothesis that asbestos exposure is the more important factor related to the elevated values of nucleosides. It was concluded, therefore, that measuring nucleoside levels in populations at high risk of developing certain kinds of cancer may provide a useful diagnostic tool for detecting "preclinical" biochemical changes that may be predictive of future neoplastic manifestations.