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Changes in the human mitochondrial genome after treatment of malignant disease

Lookup NU author(s): Dr Theresa Wardell, Professor Patrick Chinnery, Dr Gillian Borthwick, Professor Robert Taylor, Professor Graham Jackson, Emeritus Professor Alan Craft, Professor Robert Lightowlers, Professor Doug Turnbull

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Abstract

Mitochondrial DNA (mtDNA) is the only extrachromosomal DNA in human cells. The mitochondrial genome encodes essential information for the synthesis of the mitochondrial respiratory chain. Inherited defects of this genome are an important cause of human disease. In addition, the mitochondrial genome seems to be particularly prone to DNA damage and acquired mutations may have a role in ageing, cancer and neurodegeneration. We wished to determine if radiotherapy and chemotherapy used in the treatment of cancer could induce changes in the mitochondrial genome. Such changes would be an important genetic marker of DNA damage and may explain some of the adverse effects of treatment. We studied samples from patients who had received radiotherapy and chemotherapy for point mutations within the mtDNA control region, and for large-scale deletions. In blood samples from patients, we found a significantly increased number of point mutations compared to the control subjects. In muscle biopsies from 7 of 8 patients whom had received whole body irradiation as well as chemotherapy, the level of a specific mtDNA deletion was significantly greater than in control subjects. Our studies have shown that in patients who have been treated for cancer there is an increased level of mtDNA damage. © 2002 Elsevier Science B.V. All rights reserved.


Publication metadata

Author(s): Wardell, T. M., Ferguson, E., Chinnery, P. F., Borthwick, G. M., Taylor, R. W., Jackson, G., Craft, A. W., Lightowlers, R. N., Howell, N., Turnbull, D. M.

Publication type: Article

Publication status: Published

Journal: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis

Year: 2003

Volume: 525

Issue: 1-2

Pages: 19-27

ISSN (print): 0027-5107

ISSN (electronic):

URL: http://dx.doi.org/10.1016/S0027-5107(02)00313-5

DOI: 10.1016/S0027-5107(02)00313-5

PubMed id: 12650902


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