Deoxypyrimidine-induced inhibition of the cytokinetic effects of 1-beta-D-arabinofuranosyluracil.

Autor:	Chandrasekaran, Bangaru, Kute, Timothy, Capizzi, Robert, Chandrasekaran, B, Kute, T E, Capizzi, R L
Předmět:	CANCER chemotherapy DNA metabolism ANIMAL experimentation CELL cycle COMPARATIVE studies DNA DRUG synergism DOSE-effect relationship in pharmacology FLOW cytometry HETEROCYCLIC compounds LEUKEMIA RESEARCH methodology MEDICAL cooperation MICE NUCLEOSIDES RESEARCH RESEARCH funding TRANSFERASES EVALUATION research CYTARABINE PHARMACODYNAMICS
Zdroj:	Cancer Chemotherapy & Pharmacology; Nov1992, Vol. 29 Issue 6, p455-460, 6p
Abstrakt:	Ara-U-induced S-phase accumulation and the interaction between high concentrations of ara-U (HiCAU) and ara-C were investigated in L1210 leukemia cells in vitro. Treatment of exponentially growing L1210 murine leukemia cells with ara-U (200-1000 microM) for 48 h caused a dose-dependent accumulation of cells in the S-phase. The extent of this ara-U-induced S-phase accumulation correlated with ara-U incorporation into DNA and with increases of up to 172% and 464% in the specific activities of deoxycytidine kinase and thymidine kinase, respectively, over control values. Metabolism of 1 microM ara-C following the exposure of cells to ara-U (1 mM) resulted in 4.5 pmol araC DNA/mg protein vs 2.1 pmol/mg protein in control cells. Although 48-h exposure of cells to 200 and 400 microM ara-U is not cytotoxic, it enhances the cytotoxicity of ara-C (10-100 microM) 4- to 10-fold. Ara-U-induced S-phase accumulation is inhibited by deoxypyrimidine nucleosides but not by pyrimidine or deoxypurine nucleosides. Some of the ara-U and ara-C concentrations used in this study are achievable in clinical practice, and ara-U/ara-C interactions may explain in part the unique therapeutic utility of high-dose ara-C. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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