Altered excretion of modified nucleosides and beta-aminoisobutyric acid in subjects with acquired immunodeficiency syndrome or at risk for acquired immunodeficiency syndrome.

Urinary excretion of modified nucleosides and beta-aminoisobutyric acid, subsequently referred to as markers, was determined in populations of patients with acquired immunodeficiency syndrome (AIDS) or at risk for development of AIDS. Our results show that asymptomatic adult male homosexuals excreted elevated amounts of markers as compared to male heterosexuals. This aberrant excretion was more pronounced in asymptomatic adult male homosexuals with antibodies to HTLV-III. Significantly greater excretion of 1-methylinosine, N4-acetylcytidine, and N2-methylguanosine was observed in asymptomatic adult male homosexuals with antibodies to HTLV-III than in asymptomatic male homosexuals without antibodies to HTLV-III. Increased amounts of markers were also excreted by subjects with the generalized or chronic lymphadenopathy syndrome, AIDS related complex (ARC), or AIDS. In these subjects, the most pronounced differences between groups were between subjects with chronic lymphadenopathy syndrome and those with ARC; subjects with ARC excreted greater amounts of seven of the ten urinary markers. There were few differences between subjects with ARC and those with AIDS, Kaposi's sarcoma, or AIDS with opportunistic infections. This observation may be useful for identifying subjects who are at risk of developing AIDS. A prospective study to test this hypothesis is under way.

Elevated urinary excretion of beta-aminoisobutyric acid and exposure to inorganic lead.

beta-Aminoisobutyric acid (beta-AIB), a normal degradation product of thymine, a constituent of DNA and, to a lesser extent, of transfer RNA, is excreted in low levels in human urine. We found that a group of iron workers occupationally exposed to inorganic lead excreted high levels of urinary beta-AIB. Elevated urinary excretion of beta-AIB was also observed in marmosets, Callithrix jacchus, that received lead acetate in drinking water. Our results suggest that increased urinary excretion of beta-AIB could stem from damage to DNA on exposure to lead.

Urinary excretion of modified nucleosides in patients with acquired immune deficiency syndrome (AIDS) and individuals at high risk of AIDS.

Patients with certain malignant diseases excrete in their urine elevated levels of modified nucleosides originating from breakdown of transfer RNA (tRNA). A high incidence of acquired immune deficiency syndrome (AIDS), often associated with rapidly progressing Kaposi's sarcoma (KS), is currently being observed in many countries. Male homosexuals are considered to be at highest risk of developing these disorders. We have examined 10 patients with AIDS and 77 male homosexuals without clinical manifestations of AIDS at the time of examination. Elevated levels of modified nucleosides were found in all patients with AIDS. Of further interest was the finding of a high prevalence of abnormal nucleoside levels in the high-risk group, with a trend toward higher levels in those high-risk individuals who had lymphadenomegaly, considered a prodrome of AIDS. These findings indicate that determination of urinary nucleoside levels may help identify individuals at high risk of developing AIDS thereby increasing the possibility for prevention and early therapy.

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.