Abstract
EICAR (5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide) is a cytostatic agent that inhibits murine leukemia L1210 and human lymphocyte CEM cells at a 50% inhibitory concentration of 0.80-1.4 microM, respectively. EICAR causes a rapid and marked inhibition of inosinate (IMP) dehydrogenase (EC 1.1.1.205) activity in intact L1210 and CEM cells reflected by a concentration-dependent accumulation of IMP and depletion of GTP and dGTP levels. EICAR 5'-monophosphate is a potent inhibitor of purified L1210 cell IMP dehydrogenase (Ki/Km 0.06). Inhibition of IMP dehydrogenase by EICAR 5'-monophosphate is competitive with respect to IMP. L1210 cells that were selected for resistance to the cytostatic action of EICAR proved to be adenosine kinase-deficient. Also, studies with other mutant L1210 and CEM cell lines revealed that adenosine kinase, as well as an alternative pathway, may be responsible for the conversion of EICAR to its 5'-monophosphate. Purified 2'-deoxycytidine kinase, 2'-deoxyguanosine kinase, cytosolic 5'-nucleotidase, and nicotinamide dinucleotide (NAD) pyrophosphorylase do not seem to be markedly involved in the metabolism of EICAR.
Highlights
EICAR (5-ethynyl-l-~-~-ribofuranosylimidazole-4in-ferred that its mode of action must be similar to that of carboxamide)is a cytostatic agent that inhibits murine ribavirin [1].Ribavirin has been identified as an inhibitor of leukemia L1210 and human lymphocyte CEM cells at IMP dehydrogenase [3,4,5,6]
EICAR 5’-monophosphate is a potent inhibitor of purified L1210 cell IMP dehydrogenase (KJK,0.06).Inhibition of IMP dehydrogenase by EICAR 5’-monophosphateis competitive with respect to IMP.L1210 cellsthat were selected for resistance to the cytostatic action of EICAR proved to reduction in the guanine nucleotide pool levels
We have investigated the mode of antiosine kinase, as well as an alternative pathway, may metabolic action of EICARin L1210 andCEM cells
Summary
0 1993 by The American Society for Biochemistry and Molecular Biology, Inc. Vol 268, No 33, Issue of November 25, pp. 24591-24598,1993 Printed in U.S.A. EICAR (5-ethynyl-l-~-~-ribofuranosylimidazole-4in-ferred that its mode of action must be similar to that of carboxamide)is a cytostatic agent that inhibits murine ribavirin [1].Ribavirin has been identified as an inhibitor of leukemia L1210 and human lymphocyte CEM cells at IMP dehydrogenase [3,4,5,6]. EICAR 5’-monophosphate is a potent inhibitor of purified L1210 cell IMP dehydrogenase (KJK,,,0.06).Inhibition of IMP dehydrogenase by EICAR 5’-monophosphateis competitive with respect to IMP.L1210 cellsthat were selected for resistance to the cytostatic action of EICAR proved to reduction in the guanine nucleotide pool levels. The deoxyguanosine kinase, cytosolic 5’-nucleotidase, and 5’-monophosphate of EICAR(EICAR-MP) was foundto nicotinamide dinucleotide (NAD) pyrophosphorylase markedly inhibit purified L1210 IMP dehydrogenase. Do not seem to be markedly involved in the metabolism of EICAR
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
