Polyvinyl Pyrrolidone Promotes DNA Cleavage by a ROS-Independent and Depurination Mechanism

Abstract

Polyvinyl pyrrolidone polymer (PVP) has been widely applied in biological and medical fields. A few in vitro studies indicated that PVP might cause toxicity. However, the underlying mechanism is poorly understood. In this work, we found that PVP directly induced strand breakages of various DNA molecules, implicating a cleavage activity. Moreover, reactive oxygen species (ROS) scavenging analysis shows that DNA cleavage activity of PVP is not related to ROS-induced oxidation. As revealed by gel electrophoresis and liquid chromatography/mass spectrometry analysis, the major cleavage products of DNA were identified as two purine bases, guanine and adenine, suggesting that PVPs have a novel depurination activity. The selective depurination and DNA cleavage activity of PVPs were further confirmed by studying the interaction of PVP with four nucleosides and four well-designed oligodeoxynucleotides probes containing specific nucleotides. This study may provide insights into PVP-DNA interactions and resultant genotoxicity and may also open a new way for DNA study.

Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation

“…27 Quantifying the amount of pDNA that could be delivered in vivo was determined via application of RALA/pDNA-loaded microneedle arrays to mouse ears for 24 h. Using this formulation we were able to load and deliver larger quantities of pDNA than other dissolvable devices previously reported, without compromising mechanical integrity. 34,35,53,54 Of our formulations, 9-10 kDa PVA microneedle arrays were found to contain significantly higher amounts of pDNA in the baseplate and needles than 360 kDa PVP, 58 kDa PVP, and 13-23 kDa microneedle arrays, and subsequently delivered the greatest quantity of pDNA in vivo. Therefore the evidence from this study indicates that 9-10kDa PVA was the optimal polymer for fabrication of RALA/pDNA-loaded microneedle arrays.…”

“…PVP has been previously reported to cause cleavage of DNA by hydrolysis of guanine and adenine bases. 53 During the formulation process it was observed that pDNA incorporated into PVA and PVP matrices also underwent a change in structure. To achieve high transfection efficacies retaining the supercoiled conformation of pDNA is desirable.…”

Molecular Characterization of Alkaline Phosphatase and PLAP in the Germinal Epithelium of Pb and Se+Zn Treated Adult Sprague Dawley Rats

“…showed increased activities of AST, ALT and Alkaline phosphate, the effects was also consistent for hepatic, kidney and neural tissues [27,28]. Zn and Se are complementary in function, aside having synergistic effects when co-administered, as selenium supplementations have been seen to improve zinc levels and anti-oxidant value of blood [29][30][31] and counter oxidative stress better [16]; primary marker is improved membrane transport and metalloenzymes activity (CcOX & ALP) as selenium inhibits oxidative stress, improves signal transport and differentiation in bone marrow cells. Se+Zn will also generally improve the blood metabolic profile [32].…”

DNA Cleavage by Chemically Exfoliated Molybdenum Disulfide Nanosheets

“…Nanomaterials that allow gene editing or DNA cleavage might show great potential as therapeutics for human diseases such as tumors and microbial infections but may also have a negative impact on the environment. − Among the nanomaterials, carbonaceous nanomaterials show great potential for DNA cleavage with an external energy input such as photoirradiation. For example, fullerenes show strong photosensitizing activities and are able to produce reactive oxygen species (ROS) such as singlet oxygen ( 1 O 2 , with energy transfer) and superoxide anions (O 2 – , with electron transfer) that cause DNA cleavage activities and thus can be used in photodynamic therapy and antibacterial activities. − Graphene quantum dots can also enhance the DNA activity of metal ions by accelerating the formation of transient reactive radicals depending on the three-dimensional metal complexes for a highly efficient DNA cleavage activity. , However, most of them require external energy.…”