Open AccessMetabolism and Toxicity of Electroporated 1‐β‐ d ‐Arabinofuranosylcytosine Triphosphate in a Human Leukemia Cell Line
Author(s) -
Kubota Masaru,
Yorifuji Tohru,
Hashimoto Hisako,
Shimizu Tsunehiro,
Mikawa Haruki
Publication year - 1990
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1990.tb02696.x
Subject(s) - toxicity , electroporation , cell culture , deoxycytidine kinase , nucleoside , microbiology and biotechnology , biochemistry , biology , chemistry , deoxycytidine , chemotherapy , genetics , organic chemistry , gemcitabine , gene
The metabolism and toxicity of 1‐β‐ d ‐arabinofuranosylcytosine triphosphate (ara‐CTP) directly injected into cells by electroporation was studied in human leukemia cell lines. The intracellular accumulation of ara‐CTP (ara‐CTP‐Ep) was dependent on the cell type, extracellular ara‐CTP concentration and pulse voltage on electroporation. In a promyelocytic leukemia cell line, HL‐60, ara‐CTP‐Ep revealed a cytotoxic effect in a dose‐dependent manner, although electroporation alone did not have any significant toxicity. Furthermore, simultaneous injection of dCTP, or continuous exposure to deoxycytidine, but not to other deoxyribonucleosides, immediately after electroporation rescued the cells from the toxicity of ara‐CTP‐Ep. The degradation of ara‐CTP‐Ep consisted of an early rapid phase followed by a slower phase with a half life of 1.5 h. The addition of dipyridamole (10 μM), an inhibitor of nucleoside transport, retarded this degradation process. These data indicate that transfer of ara‐CTP by electroporation is a useful method for the study of ara‐CTP metabolism.