Radiation fibrosis is a frequent sequel of therapeutic or accidental radiat
ion overexposure in normal human tissues. One of the main fundamental probl
ems yet unsolved in fibrotic tissues is the origin of the chronic activatio
n of myofibroblasts within these tissues. It has been postulated that this
chronic activation results from a continuous production of activating facto
rs. In this context, fibrosis could be defined as a wound where continuous
signals for tissue repair are emitted. Cytokines and growth factors probabl
y play a central role in this process, Among them, transforming growth fact
or-beta 1 (TGF-beta 1) is considered as a master switch for the fibrotic pr
ogram. This review discusses recent evidence on the critical role played by
TGF-beta in the initiation, development, and persistence of radiation fibr
osis, It summarizes the results concerning this factor after irradiation of
various tissues and cells, with an emphasis on superficial fibrosis, inclu
ding skin and subcutaneous tissues, Finally, recent data concerning the tre
atment of established fibrotic disorders of various etiology are presented,
as well as the possible mechanisms involved in fibrosis regression, which
show that the TGF-beta pathway may constitute a specific target for antifib
rotic agents. (C) 2000 Elsevier Science Inc.