PT - JOURNAL ARTICLE AU - M S Chen AU - K L Woods AU - W H Prusoff TI - Molecular basis of the antineoplastic activity of 3'-amino-3'-deoxythymidine. DP - 1984 May 01 TA - Molecular Pharmacology PG - 441--445 VI - 25 IP - 3 4099 - http://molpharm.aspetjournals.org/content/25/3/441.short 4100 - http://molpharm.aspetjournals.org/content/25/3/441.full SO - Mol Pharmacol1984 May 01; 25 AB - 3'-Amino-3'-deoxythymidine decreased the incorporation of [2-14C]thymidine into DNA of L1210 cells in vitro, and produced an accumulation of [2-14C]thymidine di- and triphosphate. The extent of these effects varied with the amount of recovery time after removal of 3'-amino-3'-deoxythymidine prior to addition of labeled thymidine. The distribution of radioactivity in the acid-soluble fraction derived from [3H]3'-amino-3'-deoxythymidine was as follows: 50% as 3'-amino-3'-deoxythymidine, 20% as the monophosphate, 10% as the diphosphate, and 20% as the triphosphate derivatives. No incorporation of [3H]3'-amino-3'-deoxythymidine into L1210 DNA could be detected. 3'-Amino-3'-deoxythymidine-5'-triphosphate is a competitive inhibitor against dTTP with a Ki of 3.3 microM, whereas the Km for dTTP was 8 microM using activated calf thymus DNA as the template and DNA polymerase-alpha. These data indicate that a major site of inhibition by 3'-amino-3'-deoxythymidine is inhibition of the DNA polymerase reaction.