title: 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.
authors: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors: Maoyong
authors: M
authors: Song
authors: Luzhe
authors: L
authors: Zeng
authors: Xianjun
authors: X
authors: Hong
authors: Zihui
authors: Z
authors: Meng
authors: Junfa
authors: J
authors: Yin
authors: Hailin
authors: H
authors: Wang
authors: Yong
authors: Y
authors: Liang
authors: Guibin
authors: G
authors: Jiang
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D053837:DNA Cleavage / Q000187:drug effects*; D008958:Models, Molecular; D009153:Mutagens / Q000633:toxicity*; D011205:Povidone / Q000633:toxicity*; D011687:Purines / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D009153:Mutagens; D011687:Purines; D017382:Reactive Oxygen Species; D004247:DNA; D011205:Povidone