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Carcinogenesis Advance Access published online on May 27, 2004
Carcinogenesis, doi:10.1093/carcin/bgh196
© 2004 by Oxford University Press
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Received March 10, 2004
Revised April 22, 2004
Accepted May 18, 2004

COMMENTARY

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

Lorne J. Hofseth 1*

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

* To whom correspondence should be addressed. E-mail: hofseth{at}cop.sc.edu.


  Abstract

An adaptive response of the genome-protection machinery occurs in cells exposed to genotoxic stress. This machinery includes the p53 and pRb pathways, which are not mutually exclusive from other adapting machinery including DNA repair, cell cycle checkpoints, apoptosis, and endogenous metabolizing and anti-oxidant 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.

Key Words: cancer, genotoxic stress, adaptive response, inflammation, smoking


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