BIOMAT Database Logo BIOMAT Database Logo

Increased sensitivity to 1-beta-D-arabinofuranosylcytosine in P388 murine leukemic cells resistant to etoposide. 1989

M Higashigawa, and M Ido, and T Ohkubo, and H Kawasaki, and H Kamiya, and M Sakurai, and K Taniguchi, and M Hamazaki
Department of Pediatrics, Mie University School of Medicine, Japan.

A variant P388 murine leukemic cell resistant to 4'-demethylepipodophyllotoxin-9-(4,6-O-ethylidine)-beta-D-gl ucopyranoside (etoposide) (VP-16-213) was cloned. The variant P388/VP-16 cell line was 159-fold resistant to VP-16. We found that this variant P388/VP-16 cell line showed collateral drug sensitivity to 1-beta-D-arabinofuranosylcytosine(Ara-C), determined by comparing the 50% inhibitory concentrations in 48-h growth inhibition assay. To clarify the mechanism of this increased sensitivity to Ara-C, we quantified the deoxyribonucleoside triphosphate pools and 1-beta-D-arabinofuranosylcytosine triphosphate(Ara-CTP) using high-performance liquid chromatography in the parent and drug-resistant sublines of P388 cells. The analysis of deoxyribonucleoside triphosphate pools revealed that the pyrimidine triphosphate pools were significantly decreased in the P388/VP-16 cell line and the Ara-CTP concentration of two variant cell lines were not significantly different. The Ara-CTP/dCTP ratio was significantly increased in P388/VP-16 cells. These data suggest that the inhibition of the dCTP de-novo pathway and the preservation of the dCTP salvage pathway in P388/VP-16 cells might correlate with the increased sensitivity to Ara-C.

UI MeSH Term Description Entries
D007941 Leukemia P388 An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene. P388D(1) Leukemia,P388, Leukemia
D007942 Leukemia, Experimental Leukemia induced experimentally in animals by exposure to leukemogenic agents, such as VIRUSES; RADIATION; or by TRANSPLANTATION of leukemic tissues. Experimental Leukemia,Experimental Leukemias,Leukemia Model, Animal,Leukemias, Experimental,Animal Leukemia Model,Animal Leukemia Models,Leukemia Models, Animal
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003561 Cytarabine A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472) Ara-C,Arabinofuranosylcytosine,Arabinosylcytosine,Cytosine Arabinoside,Aracytidine,Aracytine,Cytarabine Hydrochloride,Cytonal,Cytosar,Cytosar-U,beta-Ara C,Ara C,Arabinoside, Cytosine,Cytosar U,beta Ara C
D003854 Deoxyribonucleotides A purine or pyrimidine base bonded to a DEOXYRIBOSE containing a bond to a phosphate group. Deoxyribonucleotide
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D005047 Etoposide A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. Demethyl Epipodophyllotoxin Ethylidine Glucoside,Celltop,Eposide,Eposin,Eto-GRY,Etomedac,Etopos,Etoposide Pierre Fabre,Etoposide Teva,Etoposide, (5S)-Isomer,Etoposide, (5a alpha)-Isomer,Etoposide, (5a alpha,9 alpha)-Isomer,Etoposide, alpha-D-Glucopyranosyl Isomer,Etoposido Ferrer Farma,Exitop,Lastet,NSC-141540,Onkoposid,Riboposid,Toposar,VP 16-213,VP-16,Vepesid,Vépéside-Sandoz,Eto GRY,Etoposide, alpha D Glucopyranosyl Isomer,NSC 141540,NSC141540,Teva, Etoposide,VP 16,VP 16 213,VP 16213,VP16,Vépéside Sandoz,alpha-D-Glucopyranosyl Isomer Etoposide
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001085 Arabinofuranosylcytosine Triphosphate A triphosphate nucleotide analog which is the biologically active form of CYTARABINE. It inhibits nuclear DNA synthesis. Ara-CTP,Arabinosylcytosine Triphosphate,Cytarabine Triphosphate,Cytosine Arabinoside Triphosphate,Ara CTP,Triphosphate, Arabinofuranosylcytosine,Triphosphate, Arabinosylcytosine,Triphosphate, Cytarabine,Triphosphate, Cytosine Arabinoside
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

Related Publications

M Higashigawa, and M Ido, and T Ohkubo, and H Kawasaki, and H Kamiya, and M Sakurai, and K Taniguchi, and M Hamazaki
Substrate-specific deoxycytidine kinase deficiency in 1-beta-D-arabinofuranosylcytosine-resistant leukemic cells.
October 1990, Cancer research,
M Higashigawa, and M Ido, and T Ohkubo, and H Kawasaki, and H Kamiya, and M Sakurai, and K Taniguchi, and M Hamazaki
Effect of homoharringtonine on the viability of murine leukemia P388 cells resistant to either adriamycin, vincristine, or 1-beta-D-arabinofuranosylcytosine.
January 1989, Cancer chemotherapy and pharmacology,
M Higashigawa, and M Ido, and T Ohkubo, and H Kawasaki, and H Kamiya, and M Sakurai, and K Taniguchi, and M Hamazaki
Relationship of 1-beta-D-arabinofuranosylcytosine in plasma to 1-beta-D-arabinofuranosylcytosine 5'-triphosphate levels in leukemic cells during treatment with high-dose 1-beta-D-arabinofuranosylcytosine.
November 1985, Cancer research,
M Higashigawa, and M Ido, and T Ohkubo, and H Kawasaki, and H Kamiya, and M Sakurai, and K Taniguchi, and M Hamazaki
Decreased phorbol ester receptor and protein kinase C in P388 murine leukemic cells resistant to etoposide.
July 1987, Cancer research,
M Higashigawa, and M Ido, and T Ohkubo, and H Kawasaki, and H Kamiya, and M Sakurai, and K Taniguchi, and M Hamazaki
Metabolism of 1-beta-D-arabinofuranosylcytosine in human leukemic cells.
October 1977, Cancer research,
M Higashigawa, and M Ido, and T Ohkubo, and H Kawasaki, and H Kamiya, and M Sakurai, and K Taniguchi, and M Hamazaki
Enhancement by hemin of the sensitivity of K562 human leukemic cells to 1-beta-D-arabinofuranosylcytosine.
March 1986, Cancer research,
M Higashigawa, and M Ido, and T Ohkubo, and H Kawasaki, and H Kamiya, and M Sakurai, and K Taniguchi, and M Hamazaki
Biochemical effects of 2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil and 2'-fluoro-5-iodo-1-beta-D-arabinofuranosylcytosine in mouse leukemic cells sensitive and resistant to 1-beta-D-arabinofuranosylcytosine.
October 1982, Cancer research,
M Higashigawa, and M Ido, and T Ohkubo, and H Kawasaki, and H Kamiya, and M Sakurai, and K Taniguchi, and M Hamazaki
Pharmacokinetics of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate in leukemic cells after intravenous and subcutaneous administration of 1-beta-D-arabinofuranosylcytosine.
May 1985, Cancer research,
M Higashigawa, and M Ido, and T Ohkubo, and H Kawasaki, and H Kamiya, and M Sakurai, and K Taniguchi, and M Hamazaki
Synergistic interaction between etoposide and 1-beta-D-arabinofuranosylcytosine.
January 1989, Advances in experimental medicine and biology,
M Higashigawa, and M Ido, and T Ohkubo, and H Kawasaki, and H Kamiya, and M Sakurai, and K Taniguchi, and M Hamazaki
Deoxyribonucleoside triphosphate pools and Ara-CTP levels in P388 murine leukemic cells treated with 1-B-D-arabinofuranosylcytosine-5'-stearylphosphate which is a newly synthesized derivative of 1-B-D-arabinofuranosylcytosine.
January 1990, Medical oncology and tumor pharmacotherapy,
Copied contents to your clipboard!