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DNA Damage and Repair in Human Cancer: Molecular Mechanisms and Contribution to Therapy-Related Leukemias
Azienda Ospedaliera Sant’Andrea, Via di Grottarossa 1035-1039, Roma 00189, Italy
Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, Roma 00161, Italy
* Author to whom correspondence should be addressed.
Received: 23 May 2012; in revised form: 12 June 2012 / Accepted: 2 July 2012 / Published: 27 July 2012
Abstract: Most antitumour therapies damage tumour cell DNA either directly or indirectly. Without repair, damage can result in genetic instability and eventually cancer. The strong association between the lack of DNA damage repair, mutations and cancer is dramatically demonstrated by a number of cancer-prone human syndromes, such as xeroderma pigmentosum, ataxia-telangiectasia and Fanconi anemia. Notably, DNA damage responses, and particularly DNA repair, influence the outcome of therapy. Because DNA repair normally excises lethal DNA lesions, it is intuitive that efficient repair will contribute to intrinsic drug resistance. Unexpectedly, a paradoxical relationship between DNA mismatch repair and drug sensitivity has been revealed by model studies in cell lines. This suggests that connections between DNA repair mechanism efficiency and tumour therapy might be more complex. Here, we review the evidence for the contribution of carcinogenic properties of several drugs as well as of alterations in specific mechanisms involved in drug-induced DNA damage response and repair in the pathogenesis of therapy-related cancers.
Keywords: therapy-related leukemia; DNA repair; chemotherapeutic drugs
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Casorelli, I.; Bossa, C.; Bignami, M. DNA Damage and Repair in Human Cancer: Molecular Mechanisms and Contribution to Therapy-Related Leukemias. Int. J. Environ. Res. Public Health 2012, 9, 2636-2657.
Casorelli I, Bossa C, Bignami M. DNA Damage and Repair in Human Cancer: Molecular Mechanisms and Contribution to Therapy-Related Leukemias. International Journal of Environmental Research and Public Health. 2012; 9(8):2636-2657.
Casorelli, Ida; Bossa, Cecilia; Bignami, Margherita. 2012. "DNA Damage and Repair in Human Cancer: Molecular Mechanisms and Contribution to Therapy-Related Leukemias." Int. J. Environ. Res. Public Health 9, no. 8: 2636-2657.