Selective sensitivity to tiazofurin of human leukemic cells

Hiremagalur N. Jayarama, Konrad Pillwein, Craig R. Nichols, Roland Hoffman, George Weber

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

This study reports the selective sensitivity to tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC-286193) of human leukemic leukocytes as compared to normal ones in bone marrow and peripheral blood samples by comparing the production of the active metabolite, thiazole-4-carboxamide adenine dinucleotide (TAD), from labeled tiazofurin and the depression of GTP concentration. When labeled tiazofurin was incubated with leukocytes obtained from healthy volunteers or from leukemic patients (acute non-lymphocytic leukemia or acute lymphoblastic leukemia), the TAD production was 27.0 +- 8.3, 551.3 +- 71.8 and 755.9 +- 94.1 pmoles/109 cells per hr, respectively. Thus, the leukemic cells produced over 20-fold higher concentrations of TAD than the normal leukocytes. Incibation with tiazofurin in leukemic leukocytes decreased the GTP pools (to 48-79%), whereas there was no change in the normal leukocytes. These results indicate a selectivity of response to tiazofurin in human normal and leukemic leukocytes. These procedure reported in this work may be suitable as a rapid predictive test for the sensitivity of leukemic leukocytes to tiazofurin. Such a diagnostic test should be helpful in identifying neoplastic cells sensitive to tiazofurin in the Phase II trials now being developed.

Original languageEnglish (US)
Pages (from-to)2029-2032
Number of pages4
JournalBiochemical Pharmacology
Volume35
Issue number12
DOIs
StatePublished - Jun 15 1986

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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    Jayarama, H. N., Pillwein, K., Nichols, C. R., Hoffman, R., & Weber, G. (1986). Selective sensitivity to tiazofurin of human leukemic cells. Biochemical Pharmacology, 35(12), 2029-2032. https://doi.org/10.1016/0006-2952(86)90737-9