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

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

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tiazofurin
Leukocytes
Guanosine Triphosphate
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Metabolites
Routine Diagnostic Tests
Bone
Blood

ASJC Scopus subject areas

  • Pharmacology

Cite this

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

Selective sensitivity to tiazofurin of human leukemic cells. / Jayarama, Hiremagalur N.; Pillwein, Konrad; Nichols, Craig R.; Hoffman, Roland; Weber, George.

In: Biochemical Pharmacology, Vol. 35, No. 12, 15.06.1986, p. 2029-2032.

Research output: Contribution to journalArticle

Jayarama, HN, Pillwein, K, Nichols, CR, Hoffman, R & Weber, G 1986, 'Selective sensitivity to tiazofurin of human leukemic cells', Biochemical Pharmacology, vol. 35, no. 12, pp. 2029-2032. https://doi.org/10.1016/0006-2952(86)90737-9
Jayarama HN, Pillwein K, Nichols CR, Hoffman R, Weber G. Selective sensitivity to tiazofurin of human leukemic cells. Biochemical Pharmacology. 1986 Jun 15;35(12):2029-2032. https://doi.org/10.1016/0006-2952(86)90737-9
Jayarama, Hiremagalur N. ; Pillwein, Konrad ; Nichols, Craig R. ; Hoffman, Roland ; Weber, George. / Selective sensitivity to tiazofurin of human leukemic cells. In: Biochemical Pharmacology. 1986 ; Vol. 35, No. 12. pp. 2029-2032.
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