ABSTRACT
1H and 31P NMR techniques were applied to study the changes in metabolite profiles in human urine resulting from radiation exposure following the Chernobyl reactor accident. In cases of acute leukemia and different accumulated doses of external radiation (from 0.20 to 4.00 Sv), the proton spectra were classified on the basis of the peaks due to N-trimethyl groups, creatinine, citrate, glycine, and hippurate. Unidentified resonances were observed between 15.9 and 21.4 ppm in six phosphorus spectra of patients with preleukemia and acute leukemia. Characteristic spectral changes were similar for external radiation and incorporation-induced internal irradiation. The spectral patterns described may serve as a criterion of radiation injury.
Subject(s)
Leukemia, Radiation-Induced/diagnosis , Magnetic Resonance Spectroscopy , Radiation Injuries/diagnosis , Urine/chemistry , Accidents , Citrates/urine , Citric Acid , Creatinine/urine , Glycine/urine , Hippurates/urine , Humans , Leukemia, Radiation-Induced/urine , Methylamines/urine , Nuclear Reactors , Radiation Injuries/urine , UkraineABSTRACT
During x-ray-induced development of malignant lymphomas in mice their urinary excretion of eight modified nucleosides was monitored and the values were compared to the results of the histological examination of the animals at time of their sacrifice. It was found that the pathologically augmented excretion of modified nucleosides begins as much as several weeks before the malignant lymphomas can be diagnosed clinically. Thus some mice had increased levels of modified nucleosides even 10 weeks before sacrifice, though at the time of sacrifice the histological investigation revealed only some small foci of reticulum cell neoplasm in their spleen. It is therefore stressed that the usefulness of the determination of urinary modified nucleosides as an early noninvasive screening test for cancer in man and as an in vivo carcinogenicity test should be evaluated.
Subject(s)
Lymphoma/urine , Nucleosides/urine , Animals , Biotransformation , Chromatography, Affinity , Chromatography, High Pressure Liquid , Leukemia, Lymphoid/etiology , Leukemia, Lymphoid/urine , Leukemia, Radiation-Induced/urine , Lymphoma/etiology , Male , Mice , Mice, Inbred C57BL , Neoplasms, Radiation-Induced/urine , RNA, Transfer/metabolism , Time Factors , Whole-Body IrradiationABSTRACT
It is known that human cancer patients exhibit an altered urinary excretion pattern of modified nucleosides and bases, that mice bearing skin tumors excrete increased amounts of various modified nucleosides and bases, and that the onset of altered excretion of modified RNA constituents precedes tumor diagnosis. We have now obtained similar results in mice for lymphoblastic leukemia induced by a single exposure to X-ray irradiation. Mice showing severe leukemic symptoms excrete severalfold amounts of modified nucleosides in their 24-hr urine, when compared with untreated controls. X-ray-treated mice, showing no visible symptoms except increased excretion rates of these RNA constituents, were sacrificed and histologically examined. (Pre)leukemic features in spleen and lymph nodes were observed. Our results provide further evidence in support of the use of RNA catabolites as a basis for the development of an early noninvasive screening method for cancer in human beings.
