Chlorpyrifos Induces the Expression of the Epstein-Barr Virus Lytic Cycle Activator BZLF-1 via Reactive Oxygen Species

Ling Zhao,Jia-La Li,Meng-Yu Liu,Peng-Xiang Zhao,Ting-Ting Wang,Xue-Mei Ma,Lei Shang,Fei Xie,Zi-Xuan Deng

doi:10.1155/2015/309125

Abstract

Organophosphate pesticides (OPs) are among the most widely used synthetic chemicals for the control of a wide variety of pests, and reactive oxygen species (ROS) caused by OPs may be involved in the toxicity of various pesticides. Previous studies have demonstrated that a reactivation of latent Epstein-Barr virus (EBV) could be induced by oxidative stress. In this study, we investigated whether OPs could reactivate EBV through ROS accumulation. The Raji cells were treated with chlorpyrifos (CPF), one of the most commonly used OPs. Oxidative stress indicators and the expression of the EBV immediate-early gene BZLF-1 were determined after CPF treatment. Our results show that CPF induces oxidative stress as evidenced by decreased malondialdehyde (MDA) level, accompanied by an increase in ROS production, DNA damage, glutathione (GSH) level, and superoxide dismutase (SOD) and catalase (CAT) activity. Moreover, CPF treatment significantly enhances the expression of BZLF-1, and the increased BZLF-1 expression was ameliorated by N-acetylcysteine (NAC) incubation. These results suggest that OPs could contribute to the reactivation of the EBV lytic cycle through ROS induction, a process that may play an important role in the development of EBV-associated diseases.

Highlights

Pesticides are widely used in almost every nation in the world
To ascertain the involvement of the reactive oxygen species (ROS) in the CPF-induced Epstein-Barr virus (EBV) transcription, 50 μM NAC was used as an antioxidant, and the results show that the expression of BZLF-1 was inhibited by NAC to some extent (Figure 3)
Our results show that the exposure of Raji cells to CPF leads to ROS production, DNA damage, lipid peroxidation, and antioxidant depletion

Summary

Introduction

The indiscriminate use of pesticides in agriculture and for public health purposes has caused serious environmental and health problems [1]. Organophosphate pesticides (OPs) are one of the most commonly used pesticides, and their toxicity to humans and other nontarget species has caused increasing concern. OPs cause several harmful effects, including genotoxicity [2], hepatic dysfunction [3], embryo toxicity, teratogenicity, neurotoxicity [4], and neurobehavioral changes. Recent studies indicate that toxic manifestations induced by OPs may be associated with the enhanced production of reactive oxygen species (ROS) [5, 6]. The antioxidant defense system protects cells from attack by ROS. Oxidative stress arises when the ROS production overwhelms the intrinsic antioxidant defenses. Excessive ROS can cause indiscriminate damage to biological molecules, leading to lipid peroxidation and protein and nucleic damage

Objectives

Methods

Conclusion