Journal Article

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

Lorne J. Hofseth

in Carcinogenesis

Volume 25, issue 10, pages 1787-1793
Published in print October 2004 | ISSN: 0143-3334
Published online October 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh196
The adaptive imbalance to genotoxic stress: genome guardians rear their ugly heads

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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.

Keywords: BER, base excision repair; Gadd, growth arrest and DNA damage-inducible; GPx, glutathione peroxidase; NO, nitric oxide; pRb, retinoblastoma protein; SOD, superoxide dismutase

Journal Article.  5865 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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