EFFECTS OF URACIL AND THYMIDINE ON THE DEVELOPMENT OF RESISTANCE TO 5-FLUOROURACIL IN PEDIOCOCCUS CEREVISIAE

Abstract

White , P. J. (Roswell Park Memorial Institute, Buffalo, N.Y.) and C. A. Nichol . Effects of uracil and thymidine on the development of resistance to 5-fluorouracil in Pediococcus cerevisiae . J. Bacteriol. 85: 97–105. 1963.—Growth of Pediococcus cerevisiae ATCC 8081 in a basal semidefined medium was inhibited by 5-fluorouracil (FU) and 5-fluoro-2′-deoxyuridine (FUDR). Addition of uracil slightly decreased sensitivity to FU, but did not affect inhibition by FUDR. Addition of thymidine alone increased sensitivity to FUDR 500-fold, but did not appreciably affect sensitivity to FU. This organism was able to grow in the presence of high concentrations of either drug when both uracil and thymidine were added to the medium. Substrains resistant to FU were developed in the basal medium, or in basal medium with added uracil, or with thymidine. The substrains developed in the presence of uracil or thymidine were not resistant when these compounds were omitted from the medium. Cross resistance to FUDR was shown only when thymidine was present. The ability to use thymidine as a growth factor in the absence of leucovorin was lost in the substrains developed in the presence of uracil, though not in the other substrains. Washed suspensions of organisms of all strains hydrolyzed FUDR to FU, the parent strain being most active in this respect. The cellular uptake of fluorouracil-2-C 14 was less in all of the resistant substrains than in the parent strain, whether or not uracil or thymidine was present during the incubation. This uptake of FU-C 14 was decreased most markedly in the substrains which became resistant to FU in the absence of uracil.