Ribonucleotide reductase activity and growth of glutathione-depleted mouse leukemia L1210 cells in vitro.
L1210 cells treated with L-buthionine-(S/R)-sulfoximine (BSO) had glutathione (GSH) and non-protein thiol levels only 15% that of control. These GSH-depleted cells grew as well as the control L1210 cells and there was no decrease in ribonucleotide reductase activity in situ as measured by the conversion of [14C]cytidine to deoxytidine nucleotides and incorporation into DNA. Further, when these BSO-stressed cells were treated with hydroxyurea or IMPY, there was no potentiation of the inhibition caused by hydroxyurea or IMPY alone. These data indicate that the glutathione/glutaredoxin system of ribonucleotide reductase is not the sole carrier of reducing equivalents from NADPH for the reduction of the 2'-position of the corresponding ribonucleoside 5'-diphosphate; and that glutathione is not critical in regenerating the tyrosyl free-radical on the M2 subunit which is destroyed by the hydroxyurea or 2,3-dihydro-1H-pyrazolo-[2,3-alpha]imidazole (IMPY) treatment.
Weckbecker
G
G
Department of Internal Medicine, University of South Florida College of Medicine, H. Lee Moffitt Cancer Center and Research Institute Tampa 33612.
Cory
J G
JG
D000818:Animals; D019328:Buthionine Sulfoximine; D002455:Cell Division; D002478:Cells, Cultured; D003562:Cytidine; D005978:Glutathione / Q000172:deficiency*; D006918:Hydroxyurea / Q000494:pharmacology; D007939:Leukemia L1210 / Q000201:enzymology* / Q000473:pathology; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D011720:Pyrazoles / Q000494:pharmacology; D012264:Ribonucleotide Reductases / Q000378:metabolism*
D011720:Pyrazoles; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D003562:Cytidine; D012264:Ribonucleotide Reductases; D005978:Glutathione; C000971:2,3-dihydro-1H-imidazo(1,2-b)pyrazole; D006918:Hydroxyurea