ADAPTIVE RESPONSE TO DNA-DAMAGING AGENTS - A REVIEW OF POTENTIAL MECHANISMS

Citation
C. Stecca et Gb. Gerber, ADAPTIVE RESPONSE TO DNA-DAMAGING AGENTS - A REVIEW OF POTENTIAL MECHANISMS, Biochemical pharmacology, 55(7), 1998, pp. 941-951
Citations number
111
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Pharmacology & Pharmacy",Biology
Journal title
ISSN journal
0006-2952
Volume
55
Issue
7
Year of publication
1998
Pages
941 - 951
Database
ISI
SICI code
0006-2952(1998)55:7<941:ARTDA->2.0.ZU;2-Z
Abstract
The study of the adaptive response, i.e. a reduced effect from a highe r challenging dose of a stressor when a smaller inducing dose had been applied a few hours earlier, has opened many new vistas into the mech anisms by which cells can adapt to hazardous environments. Although th e entire chain from the initial event, supposedly the presence of DNA damage, to the end effect, presumably improved DNA repair, has not bee n fully elucidated, many individual links have been postulated. Initia l elements-following the still unknown signal for the presence of radi ation damage-are various kinases (protein kinase C and stress-activate d protein kinases), which, in turn, induce early response genes whose products initiate a cascade of protein-DNA interactions that regulate gene transcription and ultimately result in specific biological respon ses. These responses include the activation of later genes that can pr omote production of growth factors and cytokines, trigger DNA repair, and regulate progress through the cell cycle. Indeed, there appears to be a relation between the induction of the adaptive response and the effects oi radiation and cytostatic agents on the cell cycle, although these effects, especially the G(1) delay, occur at much higher doses than the adaptive response, and one may not indiscriminately extrapola te mechanisms responsible for cell cycle changes observed at high dose s, e.g. for radiation in the order of grays, to those involved in the adaptive responses at much lower doses, i.e. some tens of milligrays. (C) 1998 Elsevier Science Inc.