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Carcinogenesis Advance Access originally published online on May 27, 2004
Carcinogenesis 2004 25(10):1787-1793; doi:10.1093/carcin/bgh196
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Carcinogenesis vol.25 no.10 © Oxford University Press 2004; all rights reserved.

COMMENTARY

The adaptive imbalance to genotoxic stress: genome guardians rear their ugly heads

Lorne J. Hofseth

Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA

Email: hofseth{at}cop.sc.edu

An adaptive response of the genome-protection machinery occurs in cells exposed to genotoxic stress. This machinery includes the p53 and retinoblastoma protein pathways, which are not mutually exclusive from other adapting machinery including DNA repair, cell cycle checkpoints, apoptosis and endogenous metabolizing and antioxidant enzymes. The adaptive changes occur in chronic inflammation and in cigarette smokers associated with a high cancer risk, and are an attempt to keep cells healthy. However, there is increasing evidence that this response may have deleterious effects. Here, key pathways that adaptively respond to genotoxic stress are reviewed and mechanisms by which this response may have pro-carcinogenic implications are discussed.


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