Effect Of Fluorined Organics In DNA Damage: Influence Of Carbon Atoms And Functional Group In Fluorined Organics

In recent years, environmental pollution has gradually become the bottleneck in the development of the world, so the relationship between environmental pollution and sustainable development has been attracted more and more attention of human. Persistent organic pollutants (POPs) mainly come from humans’production and life activities. POPs can result in serious consequences, like interfering the hormones levels and endocrine function, affecting immune and nervous system. PFOS, a kind of PFAAs, are typical POPs. DNA plays an important role in carrying genetic information and gene expression. Many researchers found that POPs could lead to the transformation of DNA conformation, and then generate genotoxicity, chromosome aberrations, even cancer.Fluorined organics are common chemicals whose hydrogen atoms are replaced by fluorine atoms. Perfluoroalkyl acids (PFAAs) and fluoroquinolones (FQs) are two typical fluorined organics, which are broadly exposed in environment. We chose DNA as target and made perfluoropentanoic acid (PFPA), perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA) as exogenous substances to investigate the mechanisms of the interaction between DNA and PFAAs, and study the relationship between genotoxic effects and the number of carbon atoms in the PFAAs. Furthermore, we selected enrofloxacin (ENFX) as another exogenous substance, compared with PFAAs, to explore the impact of the functional groups on the mechanism of toxicity of fluorined organics. The article consists of the following two parts:In the first part, due to count & viability, comet assay,8-OHdG and ROS measurement, we demonstrated that DNA damage was induced by the PFAAs treatment because of the increasing concentrations, so the genotoxicity of PFAAs increased severity in a dose-dependent manner. Overall, while at the same exposure concentration, with growth in the number of carbon atoms, the damage of DNA was more remarkable by comet indicators and 8-OHdG contents increasing. We believed that genotoxicity of PFAAs rely on their length of carbon chain; the longer, the stronger. Furthermore, we speculated that the DNA damage in mice hepatocytes may cause by oxidative stress of PFAAs.In the second part, the influence factors between PFAAs and ctDNA and the genotoxicity effects of PFAAs to ctDNA were explored at molecular level by multi-spectroscopic techniques. We found that the fluorescence intensity of ctDNA-NR system decreased regularly with increasing contents of PFAAs. Minor groove binding was the most possible mode of binding between PFAAs and DNA confirmed through various spectroscopic and thermodynamic methods, and hydrogen bonding and van der Waals’forces were the main combining modes.In the third part, we chose ENFX as FQs representative compound to investigate the influence by functional group of fluorinecontaining compound on DNA. DNA could cause the fluorescence quenching of ENFX which confirmed as static quenching, and the quenching depend on concentrations of DNA. According to various spectroscopic and thermodynamic methods, we found that intercalative binding between ENFX and ctDNA is most possible. Hydrogen bonding and van der Waals’forces were the main combining forces. This result may associate with plane conjugated aromatic ring in ENFX.The results of our research indicate that the genotoxicity of fluorined organics increased severity in a dose-dependent manner. The toxicity of homologues relies on their length of carbon chain; the longer, the stronger. Overall, functional groups play an important role in the toxicity of fluorined organics which have different structures, because functional groups could affect the binding modes between DNA and fluorined organics.