Studies on the mechanisms of inhibition of L1210 cell growth by 3,4-dihydroxybenzohydroxamic acid and 3,4-dihydroxybenzamidoxime.
Didox and Amidox inhibit L1210 cell growth in culture. At least one of the mechanisms in the mode(s) of action of the compounds is directed at the ribonucleotide reductase site. Partially purified preparations of ribonucleotide reductase activity are inhibited by Amidox and Didox. The formation of deoxycytidine nucleotides from [14C]cytidine in intact L1210 cells is also blocked. Didox and Amidox cause the decrease in the intracellular pools of the four dNTPs. Hydroxyurea-resistant L1210 cells are not cross-resistant to either Didox or Amidox. These data suggest that Didox and Amidox are not inhibiting ribonucleotide reductase through a mechanism similar to hydroxyurea.
Tihan
T
T
Department of Internal Medicine, University of South Florida College of Medicine, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612.
Elford
H L
HL
Cory
J G
JG
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D003562:Cytidine / Q000378:metabolism; D003854:Deoxyribonucleotides / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology*; D006918:Hydroxyurea / Q000494:pharmacology; D007700:Kinetics; D007939:Leukemia L1210 / Q000378:metabolism*; D051379:Mice; D010091:Oximes / Q000494:pharmacology*; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D003854:Deoxyribonucleotides; D006877:Hydroxamic Acids; D010091:Oximes; D003562:Cytidine; C070491:Amidox; D012264:Ribonucleotide Reductases; C035419:3,4-dihydroxybenzohydroxamic acid; D006918:Hydroxyurea