期刊
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
卷 793, 期 -, 页码 15-21出版社
ELSEVIER
DOI: 10.1016/j.mrfmmm.2016.10.002
关键词
Cell-free nucleic acids; Circulating nucleic acids; Illegitimate genomic integration; DNA mutagenesis; DNA damage and apoptosis; Ageing and cancer
资金
- Department of Atomic Energy, Government of India, through its grant CTCTMC
There is extensive literature to show that nucleic acids can be taken up by cells under experimental conditions and that foetal DNA can be detected in maternal tissues. The uptaken DNA can integrate into host cell genomes and can be transcribed and translated into proteins. They can also cause chromosomal damage and karyotype alterations. Cell-free nucleic acids (cfNAs)-based non-invasive DNA diagnostic techniques are being extensively researched in the field of cancer with the potential to advance new prognostic parameters and direct treatment decisions. However, whether extracellular cfNAs that are released into circulation from dying cells as a consequence of normal physiology have any functional significance has not been explored. A recent study has demonstrated that circulating cfNAs have the ability to cause DNA damage and mutagenesis by illegitimately integrating into healthy cells of the body, thereby acting as mobile genetic elements. Fluorescently-labeled cfNAs isolated from sera of cancer patients and healthy volunteers were shown to be readily taken up by host cells followed by activation of a DNA-damage-repair-response which led their large scale integration into the host cell genomes. The latter caused dsDNA breaks and apoptosis in cells in vitro and in those of vital organs when injected intravenously into mice. Cell-free chromatin was consistently more active than cell-free DNA, while cfNAs derived from cancer patients were significantly more active than those from healthy volunteers. This study suggests that circulating extracellular cfNAs act as physiological continuously arising DNA mutagens with implications for ageing, cancer and a host of other degenerative human pathologies. (C) 2016 Elsevier B.V. All rights reserved.
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