2024-03-29T08:58:18Z
https://niigata-u.repo.nii.ac.jp/oai
oai:niigata-u.repo.nii.ac.jp:00006645
2022-12-15T03:39:58Z
453:456
471:537:568:649
Characteristics of 6-Mercaptopurine-Resistant L1210 Cells Newly Developed by in vivo and in vitro Treatment with 6-Mercaptopurine
Characteristics of 6-Mercaptopurine-Resistant L1210 Cells Newly Developed by in vivo and in vitro Treatment with 6-Mercaptopurine
Natsuno, Tetsuya
53799
Saito, Kazuko
53800
Mitsuhashi, Susumu
53801
6-Mercaptopurine-resistant sublines of L1210 cell were obtained by in vivo and in vitro treatment with 6-mercaptopurine. These 27 sublines were classified into high- and low-resistant sublines. The MAC level of the high-resistance group was 0.3 μg/ml, and that of the low-resistance group was 0.3-1 μg/ml. The sensitive parental cells showed a MAC of 0.003 μg/ml. Most of the resistant sublines kept their MAC levels stable even after 9 months of serial subcultures in a drug-free medium, though some sublines changed their MAC levels. The level of [^<14>C] 6-MP incorporation by high-resistant cells was the lowest among three types of subline, that of the sensitive cells was the highest, and that of the low resistant cells was intermediate. The thioinosinate level of the sublines was estimated by Dowex-1 column chromatography. More thioinosinate was found in cell-free lysate of the resistant subline than in the sensitive subline. Activity of hypoxanthine guanine phosphorybosyl-transferase in cell-free lysate was also estimated. These sublines showed the same level of enzyme activity in contrast to the difference in the thioinosinate level. Both the 6-MP-resistant and cytosine-D-arabinofuranocide (ara-C)-resistant cells were examined reciprocally for incorporation of 6-MP and ara-C. Neither resistant sublines incorporated the corresponding drug, thus indicating that the 6-MP resistance mechanism is specific for purines. We conclude that the 6-MP resistance of the L1210 cell is due to a defective situation of cell membrane permeability or to an active exclusion system of metabolite.
departmental bulletin paper
Niigata University School of Medicine
1989-09
application/pdf
Acta medica et biologica
2
37
63
70
Acta medica et biologica
AA00508361
05677734
https://niigata-u.repo.nii.ac.jp/record/6645/files/37(2)_63-70.pdf
eng