(1) 中国科学院海岸带环境过程与生态修复重点实验室中国科学院烟台海岸带研究所山东省海岸带环境过程重点实验室

Phosphorus flame retardants,the substitutes for brominated flame retardants,have been widely used in plastics,rubber and other materials.The potential toxic effects of organophosphate flame retardants (OPFRs) on the human body have also attracted widespread attentions from researchers home and abroad.The kidney is a crucial organ for the body eliminating toxicants.The damage of kidney cells may disrupt the normal function of the kidney.In this study,triphenyl phosphate (TPP) and tris(2-chloroisopropyl) phosphate (TCPP) were tested to investigate the mechanisms of apoptosis for human embryonic kidney cell 293 (HEK293).The key target gene p53 was screened by traditional toxicology experiments.Molecular docking and spectroscopic methods showed that TPP and TCPP could inert into the p53-DNA with intercalation and groove bindings.By disrupting the double helix structure of p53 gene fragments and activating molecular initiation events,the expression of related genes (Bax,Hrk,Bcl-2 and Bad) were affected,leading to the release of cytochrome c (cyt c) by mitochondrial pathway.Release of cyt c ultimately activate Caspase 7 to achieve cell apoptosis.This study provided basic data to research the toxic mechanism of phosphorus flame retardants.