ici-198583 and 2--deoxyadenosine-triphosphate

ici-198583 has been researched along with 2--deoxyadenosine-triphosphate* in 1 studies

Other Studies

1 other study(ies) available for ici-198583 and 2--deoxyadenosine-triphosphate

Article	Year
Inhibition of 2-desamino-2-methyl-10-propagyl-5,8-dideazafolic acid cytotoxicity by 5,10-dideazatetrahydrofolate in L1210 cells with decrease in DNA fragmentation and deoxyadenosine triphosphate pools. Biochemical pharmacology, 1991, Jul-15, Volume: 42, Issue:3 5,10-Dideazatetrahydrofolate (DDATHF) is an antifolate drug, the cytotoxic effects of which can be fully reversed by hypoxanthine, suggesting that DDATHF exerts its effects by inhibiting de novo purine biosynthesis. ICI198583 is a quinazoline based inhibitor of thymidylate synthase. In this study we examine the interaction between treatment of mouse leukaemic L1210 cells with these drugs. The addition of DDATHF with ICI198583 was correlated with a decrease in ICI198583 cytotoxicity in a dose dependent manner. This protection was associated with a decrease in DNA fragmentation, and a drop in intracellular dATP pools. These results support the hypothesis that inhibitory effects on de novo purine biosynthesis by inhibitors of dihydrofolate reductase may limit cytotoxicity, and indicate that a rise in dATP pools may be an important cytotoxic signal. Topics: Animals; Antineoplastic Agents; Cell Cycle; Cell Survival; Deoxyadenine Nucleotides; DNA, Neoplasm; Drug Antagonism; Folic Acid; Folic Acid Antagonists; Hypoxanthine; Hypoxanthines; Leukemia L1210; Mice; Tetrahydrofolates; Thymine Nucleotides; Tumor Cells, Cultured	1991

Article

Year

Inhibition of 2-desamino-2-methyl-10-propagyl-5,8-dideazafolic acid cytotoxicity by 5,10-dideazatetrahydrofolate in L1210 cells with decrease in DNA fragmentation and deoxyadenosine triphosphate pools.

Biochemical pharmacology, 1991, Jul-15, Volume: 42, Issue:3

5,10-Dideazatetrahydrofolate (DDATHF) is an antifolate drug, the cytotoxic effects of which can be fully reversed by hypoxanthine, suggesting that DDATHF exerts its effects by inhibiting de novo purine biosynthesis. ICI198583 is a quinazoline based inhibitor of thymidylate synthase. In this study we examine the interaction between treatment of mouse leukaemic L1210 cells with these drugs. The addition of DDATHF with ICI198583 was correlated with a decrease in ICI198583 cytotoxicity in a dose dependent manner. This protection was associated with a decrease in DNA fragmentation, and a drop in intracellular dATP pools. These results support the hypothesis that inhibitory effects on de novo purine biosynthesis by inhibitors of dihydrofolate reductase may limit cytotoxicity, and indicate that a rise in dATP pools may be an important cytotoxic signal.

Topics: Animals; Antineoplastic Agents; Cell Cycle; Cell Survival; Deoxyadenine Nucleotides; DNA, Neoplasm; Drug Antagonism; Folic Acid; Folic Acid Antagonists; Hypoxanthine; Hypoxanthines; Leukemia L1210; Mice; Tetrahydrofolates; Thymine Nucleotides; Tumor Cells, Cultured

1991