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Mechanism of natural resistance of rat ascites hepatomas to 1-beta-D-arabinofuranosylcytosine.

Authors: Shojiro Sato; Haruo Sato; Ikuo Abe; Minro Watanabe;

Mechanism of natural resistance of rat ascites hepatomas to 1-beta-D-arabinofuranosylcytosine.

Abstract

The biochemical basis for natural resistance to 1-beta-D-arabinofuranosylcytosine (ara-C) was investigated in the intact cells of 4 rat ascites hepatomas, AH-66F, AH-60C, AH-109A, and AH-66, whose sensitivity to ara-C was different in that decreasing order. The initial rapid uptake of ara-C, mediated by the facilitated diffusion, was similar in all the cell lines tested but the subsequent slow uptake due to phosphorylation of ara-C was inversely correlated with their drug resistance. The capacity for drug phosphorylation was slightly higher in AH-66F and much lower in AH-60C, AH-109A, and AH-66 than in the host bone marrow. In contrast, mouse leukemia L-1210, one of the tumors sensitive to ara-C, phosphorylated the drug about 7 times faster than AH-66F and 4 times faster than the host bone marrow. More than 95% of phosphorylated ara-C was the triphosphate, the active form. Deamination of ara-C was not observed in any tumor or bone marrow. It is concluded that the low capacity for nucleotide formation is related to the natural resistance of rat ascites hepatomas to ara-C.

Related Organizations
Keywords

Male, Mice, Liver Neoplasms, Experimental, Cytarabine, Animals, Phosphorylation, Leukemia L1210, Rats

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
6
Average
Average
Average
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