Decreased DNA polymerase sensitivity to 1-beta-D-arabinofuranosylcytosine 5'-triphosphate in P388 murine leukemic cells resistant to vincristine.
P388 murine leukemic cells 28.6-fold resistant to vincristine were cross-resistant to doxorubicin and etoposide. Although the intracellular ara-CTP in P388 murine leukemic cells resistant to vincristine (P388/VCR) was significantly higher than that in the parent cells, the cytotoxic effect of ara-C was not significantly different between the parent and resistant cells. Therefore, we investigated the DNA synthesis in P388/VCR and its parent cell line using the permeable cell system. The DNA synthesis in P388/VCR cells was less sensitive to ara-CTP and dTTP than that in P388 parent cells. These results suggested that the characteristics of DNA polymerase in P388/VCR cells might change when the cells developed multiple drug resistance.
Higashigawa
M
M
Department of Pediatrics, Mie University School of Medicine, Japan.
Ido
M
M
Nagao
Y
Y
Kuwabara
H
H
Hori
H
H
Ohkubo
T
T
Kawasaki
H
H
Sakurai
M
M
D000818:Animals; D001085:Arabinofuranosylcytosine Triphosphate / Q000378:metabolism*; D015153:Blotting, Western; D003561:Cytarabine / Q000633:toxicity; D004259:DNA-Directed DNA Polymerase / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D005047:Etoposide / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D007941:Leukemia P388 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D019384:Nucleic Acid Synthesis Inhibitors; D013942:Thymine Nucleotides / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000494:pharmacology*
D019384:Nucleic Acid Synthesis Inhibitors; D013942:Thymine Nucleotides; D003561:Cytarabine; D001085:Arabinofuranosylcytosine Triphosphate; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D004259:DNA-Directed DNA Polymerase; C024157:thymidine 5'-triphosphate