Thymidine concentrations in human sera: Variations in patients with leukaemia and megaloblastic anaemia

Abstract

Thymidine concentrations have been measured in human sera by radioimmunoassay using an antibody raised in rabbits with a conjugate of 1-β- d ribofuranosyl thymine and human serum albumin. The mean level in 234 normal blood donors was 0.36 μM (range 0.10–1.16 μM). In 154 patients with leukaemia and lymphoma, the mean serum thymidine level was significantly raised (mean 0.61 μM; range <0.1–7.4 μM). There was no significant difference between the different subgroups of leukaemia or lymphoma but each group was significantly raised compared to normal. In 63 patients with untreated megaloblastic anaemia, the mean serum thymidine level was also significantly raised ( P < 0.01, mean 0.47 μM, range 0.1–1.64 μM). The source of thymidine in human serum is not known but it is suggested that release from cells dying in the bone marrow and from red cell maturation in bone marrow with extrusion of nuclei may be important components. The thymidine concentrations in human serum indicate that thymidine salvage might be quantitatively a a major route of thymidylate synthesis in some tissues. Thymidine modulates the toxicity and therapeutic index of several nucleic acid antimetabolites, and variations in serum thymidine levels in different patients may influence tumour sensitivity and the toxicity of antimetabolite chemotherapy.