An Enquiry Concerning the Characteristics of Cell-Free DNA Released by Cultured Cancer Cells
Non-invasive screening that utilizes cell-free DNA (cfDNA) offers remarkable potential as a method for the early detection of genetic disorders and a wide variety of cancers. Unfortunately, one of the most prominent elements delaying the translation of cf
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An Enquiry Concerning the Characteristics of Cell-Free DNA Released by Cultured Cancer Cells Abel Jacobus Bronkhorst, Johannes F. Wentzel, Janine Aucamp, Etresia van Dyk, Lissinda H. du Plessis, and Piet J. Pretorius Abstract
Non-invasive screening that utilizes cell-free DNA (cfDNA) offers remarkable potential as a method for the early detection of genetic disorders and a wide variety of cancers. Unfortunately, one of the most prominent elements delaying the translation of cfDNA analyses to clinical practice is the lack of knowledge regarding its origin and composition. The elucidation of the origin of cfDNA is complicated by the apparently arbitrary variability of quantitative and qualitative characteristics of cfDNA in the blood of healthy as well as diseased individuals. These factors may contribute to false positive/negative results when applied to clinical pathology. Although many have acknowledged that this is a major problem, few have addressed it. We believe that many of the current difficulties encountered in in vivo cfDNA studies can be partially circumvented by in vitro models. The results obtained in this study indicate that the release of cfDNA from 143B cells is not a consequence of apoptosis, necrosis or a product of DNA replication, but primarily the result of actively released DNA, perhaps in association with a protein complex. Moreover, this study demonstrates the potential of in vitro cell culture models to obtain useful information about the phenomenon of cfDNA.
A.J. Bronkhorst (*) • J. Aucamp • E. van Dyk P.J. Pretorius Centre for Human Metabolomics, Biochemistry Division, North-West University, Potchefstroom 2520, South Africa e-mail: [email protected] J.F. Wentzel • L.H. du Plessis Centre of Excellence for Pharmaceutical Sciences (PHARMACEN), North-West University, Potchefstroom 2520, South Africa © Springer International Publishing Switzerland 2016 P.B. Gahan et al. (eds.), Circulating Nucleic Acids in Serum and Plasma – CNAPS IX, Advances in Experimental Medicine and Biology 924, DOI 10.1007/978-3-319-42044-8_4
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Keywords
Cell-free DNA (cfDNA) • Apoptosis • Necrosis • Osteosarcoma • Flow cytometry
Introduction
Materials and Methods
Understanding the processes involved in the generation of cell-free DNA (cfDNA) is critical for deducing its role in biology and pathology, while advancing the translation of analyses to clinical practice. However, the origin of cfDNA still remains elusive despite the seemingly universality of it in bio-fluids. Several sources of cfDNA have been excluded including, exogenous DNA (bacterial, viral and parasitic), lysis of cells on the interface between a tumour and circulation (Sorenson 1997) and the destruction of tumour micrometastases and circulating cancer cells (Bevilacqua et al. 1998). Currently, the only remaining conceivable sources that may account for the occurrence of cfDNA are apoptosis, necrosis, or active cellular secretion (Stroun et al. 2001). Although most evidence suggests that the release of cfDNA
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