Effects of Non-thermal Plasmas on DNA and Mammalian Cells

Abstract

The application of non‐thermal (cold) plasmas in medicine holds great promise. Non‐thermal plasma devices have been used to directly ablate cells, induce apoptosis, facilitate cell transfection, lay down bioscafolds, and sterilize heat sensitive materials. Although the reactive species (RS) generated by the plasmas have been implicated in all of these processes, the biological mechanisms of action are poorly understood and the potential adverse effects largely unknown. In this work, we used a parallel electrode dielectric barrier discharge (DBD) and the atmospheric pressure glow discharge torch (APGD‐t) to assess the possible negative effects of direct and indirect plasma treatment of mammalian cells and naked DNA. HeLa cells demonstrated an oxidative stress response when placed in direct contact with the plasma. No lipid peroxidation resulted from the application of the plasma to the cells. Both plasma sources were shown to be able to fragment naked DNA in PBS and to cause DNA double‐strand breaks (DSBs). Sequencing of treated plasmid DNA introduced into electrocompetent bacterial cells showed no evidence of mutations. We conclude that the reactive nature of non‐thermal plasmas can create oxidative stresses and may have unintended negative biological effects on cells.

Differential Influence of Components Resulting from Atmospheric-Pressure Plasma on Integrin Expression of Human HaCaT Keratinocytes

“…Vandamme et al [44] detected measurable reactive oxygen species in the gas phase over the cells and in the culture medium. Recently, intracellular ROS were also detected in other human cells as in primary ocular cells (keratocytes), breast cancer cells (MCF-10A), HeLa cells, and in hepatocellular carcinoma cells (HepG2) [20, 26, 37, 55]. Highest levels of intracellular ROS were found shortly after plasma treatment and reached values of untreated control cells 24 h after plasma treatment.…”

Mechanisms of a novel anticancer therapeutic strategy involving atmospheric pressure plasma-mediated apoptosis and DNA strand break formation

“…Leduc et al (2010) claimed that apoptosis in HeLa cells was induced by direct plasma treatment via oxidative stress but not by DNA damage, as no apoptosis was observed with indirect plasma treatment in which a ROS increase was not detected even though the DNA was severely damaged. Air plasma triggered apoptosis of mouse melanoma cancer cells causing a gradual increase in the sub-G1 population with severe DNA damage and mitochondrial dysfunction (Kim et al 2010b).…”

Reactive Molecular Dynamics Simulations for a Better Insight in Plasma Medicine

“…It is clear that plasmas have beneficial effects for cancer treatment, but the underlying mechanisms, e.g., of plasma‐induced apoptosis, are not yet fully understood . It will for sure be interesting to study the interaction of ROS (which might be generated inside the cell by plasma species) with DNA, causing irreversable damage (i.e., double strand break) leading to controlled (apoptosis) or uncontrolled (necrosis) cell death . Moreover, as cancer cells seem to be able to escape from the immune system, which is recently described as a hallmark for cancer, it might also be of interest to study the interaction of plasma species with (parts of) immunocells, to investigate whether the plasma can stimulate the immune system .…”

“…Furthermore, the interaction of plasma species with the mitochondrial outer membrane will probably be very relevant, because changes in the mitochondrial outer membrane permeability stimulate the release of pro‐apoptotic agents . Last but not least, also the interaction of plasma species with the eukaryotic cell membrane will be of great interest, as this might lead to cell detachment by breaking the cell adhesion molecules, or to find out whether the plasma species can penetrate the cell membrane and form intracellular ROS or lipid peroxidation products, which will increase the membrane permeability and cause damage to the membrane proteins, until the cell membrane collapses and the cell is damaged. Likewise, the influence of the electric field and of ions originating from the plasma on cell membrane permeabilization will be interesting to study.…”

“…The fields of application include disinfection of both living tissue and non‐living surfaces (medical tools, diagnostic devices, etc treatment of skin diseases, blood coagulation, killing or apoptosis of cancer cells, and even tissue regeneration …”