Guanosine potentiates the antiproliferative effect of cytosine-beta-D-arabinofuranoside in melanoma cell lines.

Guanosine is shown to potentiate markedly the antiproliferative effect of cytosine-beta-D-arabinoside (ara-C) on B16 F10 mouse and SKMEL-28 human melanoma cell lines. Several metabolic consequences of the synergistic interaction between ara-C and guanosine on cell growth were determined in B16 F10 mouse melanoma cells. Treatment of the cells with guanosine for 24 hr resulted in an increase in the percentage of cells in the S phase of the cell cycle, a threefold increase in intracellular GTP concentration, and an increase in the incorporation of ara-C into acid-insoluble material and phosphorylated metabolites. These findings suggest that guanosine potentiates the growth-inhibitory effect of ara-C in B16 F10 melanoma cells by increasing the intracellular concentration of its active metabolites.

[1]  P. Cornaglia-Ferraris,et al.  Morphologic and phenotypic changes of human neuroblastoma cells in culture induced by cytosine arabinoside. , 1989, Experimental cell research.

[2]  Elias S. J. Arnér,et al.  Deoxycytidine kinase is constitutively expressed in human lymphocytes: consequences for compartmentation effects, unscheduled DNA synthesis, and viral replication in resting cells. , 1988, Experimental cell research.

[3]  Y. Sidi,et al.  Growth inhibition and induction of phenotypic alterations in MCF-7 breast cancer cells by an IMP dehydrogenase inhibitor. , 1988, British Journal of Cancer.

[4]  A. Novogrodsky,et al.  Differential effects of sodium butyrate and dimethylsulfoxide on gamma-glutamyl transpeptidase and alkaline phosphatase activities in MCF-7 breast cancer cells. , 1987, Experimental cell biology.

[5]  S. Howell,et al.  The intracavitary administration of cytarabine to patients with nonhematopoietic malignancies: an update. , 1987, Seminars in Oncology.

[6]  T. Okabe,et al.  Potentiation of cytotoxicity of 1-beta-D-arabinofuranosylcytosine for K562 human leukemic cells by cadeguomycin. , 1987, Cancer research.

[7]  S. Akman,et al.  Metabolism of ara-C by blast cells from patients with ANLL. , 1986, Blood.

[8]  H. Malik,et al.  Growth inhibition of murine melanoma by butyric acid and dimethylsulfoxide. , 1986, Experimental cell research.

[9]  Y. Rustum,et al.  1-beta-D-arabinofuranosylcytosine metabolism and incorporation into DNA as determinants of in vivo murine tumor cell response. , 1985, Cancer research.

[10]  T. Okabe,et al.  Enhancement of pyrimidine nucleoside uptake into K562 and YAC-1 cells by cadeguomycin. , 1985, The Journal of antibiotics.

[11]  K. Stenzel,et al.  Dimethylthiourea inhibition of melanoma cell growth in vitro and in vivo. , 1985, Journal of the National Cancer Institute.

[12]  B. Mitchell,et al.  Effects of guanine ribonucleotide accumulation on the metabolism and cell cycle of human lymphoid cells. , 1985, Cancer research.

[13]  M. Markman.  The intracavitary administration of cytarabine to patients with nonhematopoietic malignancies: pharmacologic rationale and results of clinical trials. , 1985, Seminars in oncology.

[14]  Y. Cheng,et al.  Effect of uracil arabinoside on metabolism and cytotoxicity of cytosine arabinoside in L5178Y murine leukemia. , 1985, The Journal of clinical investigation.

[15]  S. Howell,et al.  Combination intraperitoneal chemotherapy with cisplatin, cytarabine, and doxorubicin for refractory ovarian carcinoma and other malignancies principally confined to the peritoneal cavity. , 1984, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  S. Howell,et al.  Intraperitoneal cytosine arabinoside therapy in ovarian carcinoma. , 1984, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  S. Akman,et al.  Schedule-dependent enhancement of 1-beta-D-arabinofuranosylcytosine incorporation into HL-60 DNA by deoxyguanosine. , 1984, Cancer research.

[18]  M. Iigo,et al.  Relationship between antitumor effect and metabolites of 5-fluorouracil in combination treatment with 5-fluorouracil and guanosine in ascites sarcoma 180 tumor system. , 1983, Cancer research.

[19]  F. Rauscher,et al.  Biochemical and cytokinetic modulation of L1210 and HL-60 cells by hydroxyurea and effect on 1-beta-D-arabinofuranosylcytosine metabolism and cytotoxicity. , 1983, Cancer research.

[20]  M. Iigo,et al.  Potentiation of the chemotherapeutic effect of 5-fluorouracil by combination with guanosine 5'-monophosphate. , 1983, Gan.

[21]  J. F. Henderson,et al.  Comparison of purine and pyrimidine metabolism in G1 and S phases of HeLa and Chinese hamster ovary cells. , 1982, Canadian journal of biochemistry.

[22]  D. Kufe,et al.  Correlation of cytotoxicity with incorporation of ara-C into DNA. , 1980, The Journal of biological chemistry.

[23]  S. Grant,et al.  Enhancement of 1-beta-D-arabinofuranosylcytosine accumulation within L1210 cells and increased cytotoxicity following thymidine exposure. , 1980, Cancer research.

[24]  K. Paigen,et al.  A simple, rapid, and sensitive DNA assay procedure. , 1980, Analytical biochemistry.

[25]  T. W. Mak,et al.  Deoxycytidine kinase and cytosine nucleoside deaminase activities in synchronized cultures of normal rat kidney cells. , 1978, Cancer research.

[26]  K. Rai,et al.  Acute myelocytic leukemia. , 1976, Archives of internal medicine.

[27]  C. N. Coleman,et al.  Deoxycytidine kinase: properties of the enzyme from human leukemic granulocytes. , 1975, Blood.

[28]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.