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P Comi, S Ottolenghi, B Giglioni, G Migliaccio, AR Migliaccio, E Bassano, S Amadori, G Mastroberardino and C Peschle
We report that bromodeoxyuridine (BrdU) addition in semi-solid cultures of
normal adult erythroid progenitors causes a sharp rise of gamma- globin
gene expression in erythroid colonies. Control studies were carefully
carried out to exclude the possibility of toxic effects exerted by the drug
in these experimental conditions. In particular, BrdU addition induces a
sharp increase in the level of relative gamma- globin synthesis and content
in pooled BFU-E-derived colonies: this rise is clearly observed in single
bursts of the mature type (largely composed of late erythroblasts) but not
in immature ones (essentially comprising early erythroblasts). Furthermore,
it is associated with an increase of the G gamma/G gamma + A gamma
synthetic ratio from adult up to fetal like values. Reactivation of
gamma-synthesis was observed even if BrdU was added to colonies composed
essentially of early erythroblasts, ie, when BrdU was added to either
bursts at day 10 of culture or late CFU-E-derived clones at day 1. These in
vitro observations indicate modulation of gamma-synthesis at the stage of
erythroblasts from normal adults. At the molecular level we suggest that
BrdU, by replacing thymidine in DNA, may inhibit the switch from a
fetal-like biosynthetic program expressed in early erythroblastic
differentiation to the adult program expressed in later stages of
maturation.
This article has been cited by other articles:
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| Copyright © 1986 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
