The Uptake of Guanine, Uracil, Lysine and Glycine by Ascites Cells Pretreated With Azaserine and 6-Thioguanine

Synthetic purine and pyrimidine analogues have been widely studied as inhibitors of bacterial growth and as cancer chemotherapeutic agents. A number of these compounds, e.g. fluorouracil (Chaudhuri, Montag & Heidelberger, 1958) and 8-azaguanine Others, e.g. bromo-and iodo-deoxyuridine, have been shown to be incorporated into DNA (Hakala, 1959; Prusoff, 1959), and in small amounts 6-mercapto- purine appeared to be incorporated into both RNA and DNA (Bieber, Dietrich, Elion, Hitchings & Martin, 1961). In addition to their ability to become incorporated into nucleic acids, such substances may interfere with specific steps in nucleic acid synthesis. Thus iododeoxyuridine inhibits the incorporation of either [14C]formate or [14C]orotate into DNA thymine Fluorodeoxyuridine, which is interconvertible with fluoro- uracil, acted as a powerful inhibitor of thymidylate synthetase in addition to being incorporated (as fluorouracil) into RNA (Cohen, Flaks, Barner, Loeb & Lichenstein, 1958; Habers, Chaudhuri & Heidelberger, 1959). Many similar examples appear in the literature. There have also been many suggestions that RNA containing abnormal bases has a diminished capacity for the synthesis of specific proteins or produces proteins with altered amino acid sequences