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AraC and AraCDP-L-dipalmitin uptake by mouse leukemia cells

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:6076595
1-..beta..-D-Arabinofuranosylcytosine (araC) is rapidly taken up by araC-sensitive mouse leukemia cells L1210/0 and P388/0 at 2.17 and 3.78 pmoles/min/10/sup 6/ viable cells, respectively. These sensitive cell-lines also had dC-kinase of 10-98 pmoles/min/mg soluble protein. After 1 hr of araC uptake by L1210/0 less then 5% was AraC and about 80% was araCTP. In contrast P388/0 contained 17% and 38% as araC, and 5.1% and 59% as araCTP, respectively. The araC-resistant cell-lines L1210/araC/(A) and P388/araC took up very little AraC, 0.10-0.13 pmoles/min/10/sup 6/ viable cells, had negligible dC-kinase, and contained 50% or more of drug as araC. Fresh L1210/araC/(B) cells exhibited a week resistance to araC, but they had a high uptake rate, high dC-kinase, and good phosphorylation of nucleoside like the sensitive cells. However, after maintaining these cells in mice for 1 yr the L1210/araC/(B) changed to highly araC-resistant cells that tookup little araC and have negligible dC-kinase. (5-/sup 3/H)Arabinofuranosylcytosine-5'-diphosphate-dipalmitin (araCDP-L-dipalmitin) prevents the growth of the sensitive cells, P388/araC, and L1210/araC/(B); however it has no effect on L1210/araC/(A). All of the araC-sensitive and resistant cell-lines took up the conjugate at a very high rate, 500 to 1500 pmole/10/sup 6/ viable cells during the first minute. Little of the tritium was solubilized by extracting the cells with 0.5 N HCLO/sub 4/, but most of it was extracted from all of the cell-lines by CHCL/sub 3//sup 4//methanol/H/sub 2/O. Analyses of the CHCL/sub 3//methanol/H/sub 2/O extracts of araC-sensitive and araC-resistant cells by TLC will be discussed.
Research Organization:
Roswell Park Memorial Institute, Buffalo, NY
OSTI ID:
6076595
Report Number(s):
CONF-870644-
Conference Information:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 46:6
Country of Publication:
United States
Language:
English