Application of an in vitro assay for serum thymidine kinase: Results on viral disease and malignancies in humans

Abstract

An improved method for the detection of deoxythymidine kinase (TK) in human sera is reported. The method which utilizes 125I-iododeoxyuridine (IdUrd) as a substrate was used to measure TK in sera from patients with different diseases. Sera collected during the acute stage of infectious mononucleosis were found to contain elevated levels of TK, in most cases 10-40 times the normal value. The serum TK activity disappeared gradually and reached a normal level within 4 weeks. Sera from patients with other viral infections contained in most cases normal serum TK levels except in connection with measles, rubella, varicella, herpes simplex virus and cytomegalovirus infections. Additional studies revealed that sera from patients with different types of advanced lymphomas, acute leukemias, chronic granulocytic leukemia and lung cancer of the small-cell type with metastases, contained high TK levels which fluctuated in parallel with alterations in activity of the disease. The TK activity in sera from patients with both mononucleosis and tumor disease was characterized by electrophoresis and by its ability to utilize cytidine triphosphate as the phosphate donor. The results showed that the serum TK has the same properties as the human cytosolar TKI, except in connection with varicella.

Thymidine kinase in breast cancer

“…However, age-matched subgroups of the controls, operable and systemic breast cancer patients were analysed for serum total TK (Table II). (Gronowitz et al, 1984).…”

Thymidine kinase in epithelial ovarian cancer: Relationship with the other pyrimidine pathway enzymes

“…TK and TS are highly expressed in rapidly proliferating tissues, including malignant cells, because of their DNA replication functions. 16,29 TP is elevated in cancer tissues showing such typical microenvironmental characteristics as hypoxia and low pH. 32,33 Downregulation of DPD has been reported in some malignant conditions, such as cancers of the liver and colon.…”

“…Cytosols used for TK activity assays were prepared in TRIS homogenization buffer (10 mM TRIS-HCl, 1.5 mM Na 2 EDTA, 0.5 mM DTT, 10 mM sodium molybdate and 10% glycerol, pH 7.4), as described previously by Romain et al 28 Cytosolic TK activity was determined by the method of Gronowitz et al, 29 using the commercially available radioenzymatic assay Prolifigen TK kit (Daiichi, Tokyo, Japan). Samples were incubated with ATP and 125 I-labeled iododeoxyuridine as substrate at 37°C for 4 hr.…”

“…The prognostic effect of TK is thought to depend mainly on rapid tumor cell proliferation since TK is involved in salvage DNA synthesis. 29 Cytosolic TK activity has been strongly associated with the S-phase fraction by flow cytometry in breast cancer. 11 High growth fraction, which was mainly derived from the S-phase fraction, has been shown to be an adverse prognostic factor for patients with epithelial ovarian cancer.…”

Diagnostic value of soluble interleukin-2 receptor in patients with lymphoproliferative diseases

“…Такой способ синтеза dТМР типичен лишь для интенсив-ного деления клеток в эмбриогенезе и при опухолевом росте [6]. Это позволило предположить, что уровень ТК-1 в сыворотке крови (СК) может служить мерой активно-сти клеточной пролиферации, а следовательно, степени агрессивности опухолевого процесса, в частности при ЛПЗ, а также при других злокачественных новообразова-ниях: раке молочной железы, шейки матки, мочевого пу-зыря, предстательной железы и колоректальном раке [7][8][9][10][11]. Ранее нами было показано, что ТК-1 обладает доста-точно высокой диагностической чувствительностью для ЛПЗ (неходжкинских лимфом -НХЛ и лимфогранулема-тоза -ЛГМ) -более 80,0% [12].…”