Cell cycle effects of trimetrexate (CI-898).

Autor:	Hook, Kenneth, Nelson, James, Roberts, Billy, Griswold, Daniel, Leopold, Wilbur, Hook, K E, Nelson, J M, Roberts, B J, Griswold, D P, Leopold, W R
Předmět:	CANCER chemotherapy LEUKEMIA ANIMAL experimentation ANTINEOPLASTIC agents CELL culture CELL cycle CELL physiology COLCHICINE COMPARATIVE studies DRUG design CLINICAL drug trials FLOW cytometry FOLIC acid antagonists HAMSTERS HETEROCYCLIC compounds INJECTIONS RESEARCH methodology MEDICAL cooperation METHOTREXATE MICE OVARIES RESEARCH TUMORS EVALUATION research PHARMACODYNAMICS
Zdroj:	Cancer Chemotherapy & Pharmacology; Mar1986, Vol. 16 Issue 2, p116-120, 5p
Abstrakt:	The cell cycle phase specificity of trimetrexate (CI-898) was examined. CHO cells synchronized by mitotic selection were exposed to 50 microM trimetrexate for 2 h at various time points after release from Colcemid block. Only S phase cells were sensitive to trimetrexate when survival was measured by a cloning assay. Comparison of plateau phase and log phase cultures indicated that plateau phase CHO cells were relatively insensitive to 5 microM trimetrexate. Exponentially growing L1210 cells were continuously exposed to either 30 nM or 3 nM trimetrexate and analyzed by DNA flow cytometry. Incubation with 30 nM trimetrexate produced cell cycle arrest in late G1 or early S phase, while exposure to 3 nM trimetrexate caused only a delay in progression through S phase. In an in vivo schedule dependence study with mice bearing approximately 3 X 10(6) P388 leukemia cells, trimetrexate was most effective with frequent administration. Mice treated on the optimal schedule, every 3 h X 8 on days 1, 5, and 9 after tumor implant, had life-span increases in excess of 100%. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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