Blood Plasma Pseudouridine in Patients with Malignant Proliferative Diseases

Abstract

The blood plasma concentration of pseudouridine was estimated in 104 healthy adult subjects, and 108 patients suffering from malignant proliferative diseases. The HPLC method for simultaneous determination of pseudouridine and creatinine was applied.The average physiological concentration of pseudouridine in blood plasma was 2.43 ± 0.97 μπιοί -I" 1 or 29.15 + 7.40 mmol · mol" 1 creatinine. The physiological urinary excretion of pseudouridine was 14.32 ± 5.20 μπιοί -24h" 1 · kg~°· 75 or 19.60 + 5.22 mmol -mol" 1 creatinine. Renal clearance of pseudouridine and endogenous creatinine were 4.04 + 0.99 and 5.50 ± 1.46ml -kg" 075 , respectively. A positive correlation (r = 0.55, P < 0.01) was found between age (in the range 20 -92 years) and blood plasma pseudouridine concentration (μιηοΐ · I" 1 ). By expressing plasma pseudouridine in relation to plasma creatinine, the apparent influence of non-metabolic factors (age, renal insufficiency, blood dilution) on the plasma pseudouridine concentration were largely excluded.Among haematological proliferative diseases the highest values of plasma pseudouridine concentrations were observed in chronic lymphocytic leukaemia (8.19 μπιοί-I" 1 ; 54.9 mmol -mol"" 1 creatinine) and multiple myeloma (7.02 μπιοί · I" 1 ; 52.5 mmol · mol~J creatinine). In multiple myeloma, but not in chronic lymphocytic leukaemia, the plasma pseudouridine concentration depended on the clinical stage. A lower, but still significant response in non^Hodgkin's lymphoma was noted (4.03 μπιοί · I" 1 ; 40.88 mmol · mol" 1 creatinine).A significant increase of the plasma pseudouridine concentration was characteristic of adenocarcinomas of the large intestine, and it occurred in the early stages of malignant growth. In patients with lung cancer the plasma pseudouridine concentration was elevated only in advanced cases with metastases. The increased pseudouridine concentration was evident in all examined cancers of the urogenital system: cancer of the urinary bladder, cancer of the kidney, cancer of the prostate, and cancer of the testis.It is concluded that the determination of pseudouridine in blood plasma, particularly in relation to creatinine, is a valuable biochemical m rker of accelerated turnover rate of nucleic acids associated with neoplastic growth. ') This study was supported by a grant from the Ministry of National Education.

A Novel Nucleotide Found in Human Erythrocytes, 4-Pyridone-3-carboxamide-1-β-d-ribonucleoside Triphosphate

“…Although plasma levels and urine excretion of 4PYR in our study were not performed in the same subjects to allow exact renal clearance calculations, even estimates indicate that this value is almost one order of magnitude greater than in the case of other nicotinamide metabolites or nucleosides. Renal clearance was found to be close to creatinine clearance in this study for Met4PY (data from Table 2), in our previous report for Met2PY (10), and in studies of other authors for pseudouridine (33). Such a massive accumulation of 4PYTP in the erythrocytes and 4PYR in the plasma of patients with chronic renal failure to levels that by far exceed what could be expected from reduced renal filtration suggests that there is an additional mechanism that enhances 4PYR excretion in healthy people.…”

Metabolomic and Lipidomic Profiling of Bone Marrow Plasma Differentiates Patients with Monoclonal Gammopathy of Undetermined Significance from Multiple Myeloma

“…These findings are further supported by declines in the concentration levels of sarcosine and augmentations in glycine levels detected in BM plasma of MM patients compared to that of MGUS as these biochemicals are involved in one-carbon group metabolism, which through tetrahydrofolate support purine biosynthesis and dTMP formation. These findings have been described by prior studies where the pyrimidine, pseudouridine, has been known to be in circulation in the blood at a higher level in MM patients and is an indirect measure of tRNA turnover, since it is generated from degradation of tRNA splicing intermediates 20 . Other levels of amino acids and metabolites in the BM plasma were also found to be associated with increased proliferation (S-phase >2%) of their clonal PCs in the BM (Fig.…”

Polyamines and Pyrimidines in Blood Plasma and Urine of Dogs Bearing Mammary Tumours

“…The advantage of the HPLC method applied here is a simultaneous determination of pyrimidines, purines and creatinine offering the possibility of direct calculation of plasma pyrimidines and uric acid in relation to the creatinine concentration. Such an expression of the metabolite level in blood plasma reduces variability due to nonmetabolic factors like increased absorption of water from the gastrointestinal tract, parenteral infusions, o r impaired kidney function (MOTYL et al, 1993 b).…”

“…et al, 1993 c). Pyrimidines, creatinine and uric acid in blood plasma and in urine were determined by HPLC as described earlier (MOTYL et al, 1993 a,b). Results were statistically evaluated by Student's t-test.…”

“…In spite of m a n y reports concerning application of modified nucleosides e.g. pseudouridine (MOTYL et al, 1993 a,b) or polyamines (TORMEY et al, 1980;LOSER et al, 1990) in diagnosis of h u m a n malignant proliferative diseases, there is an evident deficit of informations on the role of these tumor markers in veterinary medicine. The present paper is the first to describe blood plasma pattern of pyrimidines (pseudouridine, uridine, uracil) and uric acid as well as urinary concentrations of polyamines (spermidine, spermine) a n d pseudouridine in healthy dogs and those bearing mammary tumours.…”