Induction of macrophage apoptosis by an organochlorine insecticide acetofenate.
Acetofenate (AF) is a widely used insecticide in China and other regions of southeastern Asia. A previous study showed that AF caused adverse developmental effects in zebrafish. Macrophages, which play a key role in inflammation, host defense, and reactions against a spectrum of autologous and foreign invaders, are crucial for innate immunity. However, cytotoxicity and apoptosis of macrophages caused by organochlorine pesticides (OCPs) have so far received little attention. In this study, we used AF as a model chemical to investigate the cytotoxic effects of OCPs on mouse macrophage cell line RAW264.7. Results from cell viability and apoptosis assays showed that AF induced apparent apoptosis in RAW 264.7 cells. Furthermore, AF induced intracellular reactive oxygen species (ROS) generation and DNA damage and resulted in the alteration of a series of signaling molecules including up-regulation of p53 and cytochrome c protein levels, decline of the Bcl-2/Bax protein ratio, and activation of the caspases cascade through caspase-9 and caspase-3. These results, for the first time, revealed that the increase of endogenous ROS and DNA damage comediating OCP-induced apoptosis in macrophages may be by the mitochondria and p53 signal pathway. Our results suggested that macrophages are involved in AF-induced adverse immune effects. Considering the ubiquitous environmental presence of OCPs, this study provided new information on the potential long-term physiological and immunological effects due to chronic exposures to OCPs.
Zhao
Meirong
M
Research Center of Green Chirality, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, People's Republic of China.
Zhang
Ying
Y
Wang
Cui
C
Fu
Zhengwei
Z
Liu
Weiping
W
Gan
Jay
J
D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004980:Ethane / Q000031:analogs & derivatives* / Q000633:toxicity; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism
C530171:2,2,2,-trichloro-1-(3,4-dichlorophenyl)-ethylacetate; D006843:Hydrocarbons, Chlorinated; D007306:Insecticides; D017382:Reactive Oxygen Species; D020169:Caspases; D004980:Ethane