Studies of fluorinated pyrimidines. XV. Inhibition of the incorporation of formate-C14 into DNA thymine of Ehrlich ascites carcinoma cells by 5-fluoro-2'-deoxyuridine-5'-monophosphate and related compounds.

Abstract

Summary The inhibition of the incorporation of formate into DNA thymine by 5-fluoro-2′-deoxyuridine-5′-monophosphate (FUDRP) and related compounds was studied in suspensions of Ehrlich ascites carcinoma cells in vitro . On a molar basis FUDRP was a less effective inhibitor than 5-fluoro-2′-deoxyuridine (FUDR). Esterification of the phosphate group of FUDRP decreased the inhibitory activity further. 5-Fluoro-2′-deoxyuridine-5′-triphosphate and polymers of FUDRP inhibited the incorporation slightly more than an equimolar quantity of FUDRP. The ribonucleoside and ribonucleotides of 5-fluorouracil and polymers of 5-fluorouridine-5′-monophosphate were less active inhibitors than FUDRP. Dinucleoside monophosphates of fluorinated pyrimidines were also less effective inhibitors than FUDRP. 5-Fluoro-2′-deoxycytidine was a better inhibitor of this process than FUDR. β-d-Arabinosyl-5-fluorouracil, 3′,5′-diacetyl-5-fluoro-2′-deoxyuridine, 3′-acetyl-5-fluoro-2′-deoxyuridine, 5′-trityl-5-fluoro-2′-deoxyuridine and N-[5-fluoro-2′-deoxyuridine-5′-phosphoro]-l-alanine did not inhibit the incorporation of formate-C 14 into DNA thymine of Ehrlich ascites cells to any significant extent. The probable significance of these findings is discussed.