Tiazofurin induction of mouse erythroleukemia cell hemoglobin production in
the absence of commitment or changes in protooncogene expression
ML Sherman, TD Shafman, MS Colman and DW Kufe
Laboratory of Clinical Pharmacology, Dana-Farber Cancer Institute, Boston,
MA 02115.
Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC 286193), is a
synthetic nucleoside inhibitor of inosine monophosphate dehydrogenase and
blocks guanine nucleotide biosynthesis. In the present study, we examined
the effects of tiazofurin on mouse erythroleukemia (MEL) cell
differentiation and protooncogene expression. Tiazofurin induced hemoglobin
production in MEL cells in a concentration-dependent manner, as measured by
an increase in benzidine staining. Northern blot analysis of MEL cells
treated with 7 mumol/L tiazofurin demonstrated accumulation of both alpha-
and beta-globin RNA transcripts. This induction of differentiation was
blocked by the presence of exogenous guanosine (100 mumol/L). In contrast
to the down- regulation of c-myc and c-myb RNA in MEL cells induced by
dimethyl sulfoxide (DMSO) or hexamethylene bisacetamide (HMBA), there was
no detectable change in levels of these transcripts after tiazofurin
treatment. Furthermore, MEL cells induced by tiazofurin did not commit to
terminal differentiation. These results suggest a role for guanine
nucleotides, at least in part, in the regulation of MEL cell
differentiation.
Volume 73,
Issue 2,
pp. 431-434,
02/01/1989
Copyright © 1989 by The American Society of Hematology
