Adaptive response to DNA-damaging agents: a review of potential mechanisms.
The study of the adaptive response, i.e. a reduced effect from a higher challenging dose of a stressor when a smaller inducing dose had been applied a few hours earlier, has opened many new vistas into the mechanisms by which cells can adapt to hazardous environments. Although the entire chain from the initial event, supposedly the presence of DNA damage, to the end effect, presumably improved DNA repair, has not been fully elucidated, many individual links have been postulated. Initial elements--following the still unknown signal for the presence of radiation damage--are various kinases (protein kinase C and stress-activated 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 responses. These responses include the activation of later genes that can promote 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 of radiation and cytostatic agents on the cell cycle, although these effects, especially the G1 delay, occur at much higher doses than the adaptive response, and one may not indiscriminately extrapolate mechanisms responsible for cell cycle changes observed at high doses, 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.
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Teratogenicity and Mutagenicity Unit, Catholic University of Louvain, Brussels, Belgium. Leonard@temu.ucl.ac.be
Gerber
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D000222:Adaptation, Physiological / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects*; D006801:Humans; D011506:Proteins / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D011506:Proteins