5-Hydroxymethyl-2'-deoxyuridine. Cytotoxicity and DNA incorporation studied by using a novel [2-14C]-derivative with normal and leukemic human hematopoietic cells.

Abstract

5-Hydroxymethyl-2'-deoxyuridine is a biologically active thymidine analogue. This investigation was aimed at characterizing the cytotoxicity of 5-hydroxymethyl-2'-deoxyuridine and its incorporation into DNA. Fifty percent inhibition of cellular proliferation, assessed by incorporation of [U-14C]-L-leucine in vitro, was caused by 1.7-5.8 X 10(-5) incorporation of [U-14C]-L-leucine in vitro, was caused by 1.7-5.8 X 10(-5) M 5-hydroxymethyl-2'-deoxyuridine in seven human leukemia cell lines. Higher concentrations of 5-hydroxymethyl-2'-deoxyuridine, i.e. 6-8 X 10(-5) M, were required for a comparable inhibition in human PHA-stimulated peripheral blood lymphocytes. A new synthesis procedure for [2-14C]5-hydroxymethyl-2'-deoxyuridine was developed. The net incorporation of [2-14C]5-hydroxymethyl-2'-deoxyuridine into DNA of hematopoietic cells was low. The possibility of a repair mechanism for 5-hydroxymethyluracil bound to DNA is discussed.