Studies On The Toxicity Pathways Of Typical Endocrine Disrupting Chemicals By Complex Networks

Substituted benzenes and perfluorinated compounds as the typical endocrine disrupting chemicals have strong reproductive and developmental toxicity at low doses,which are becoming one of the hot spots of research in environmental toxicology field.Substituted benzenes and perfluorinated compounds can affect signaling pathwaysof body and disturb the balance of hormones in human.Because of the particularity of structure,they can't be degraded into the human body and interfere with the body's normal signal pathway.Therefore,we need to find a complete,comprehensive and accurate methods to evaluate the toxicity of substituted benzenes and perfluorinated compounds.Complex network provides a new way to evaluate the toxicity of substituted benzenes and perfluorinated compounds because of its holistic and systematic analysis.First of all,we built a complex network formed by a compounds-target interaction database,consisting by 20 substituted benzenes endocrine disrupting chemicals and 71 targets.Six genes were obtained as the hubs genes by topological analysis and then put into the KEGG(Kyoto encyclopedia of genes and genomes)signaling pathway database.Target genes ESR2 and MMP9 present an influence on estrogen signal pathway based on complex network prediction of substituted benzene compounds.Meanwhile,target genes HIST3H3 and MMP9 appear to play a very important role of transcriptional misregulation in cancer,including prostate cancer and multiple myeloma.Among them,multiple myeloma may be a new pathway in endocrine disrupting toxicity for substituted benzenes.More importantly,the molecular dynamic was also approached aiming to understand key compound and structural features responsible for C133 compound binding with NR1I2 and MMP9 receptor.Secondly,we also built perfluorinated compounds-targets interaction network.Through the network topology analysis,we found 4 hubs genes and then put into the KEGG signaling pathway database.Target gene HSD17B1 was involved in the biosynthesis pathway of steroid hormones.The results demonstrate that gene HSD17B1 may be a new potential target in endocrine disrupting toxicity for perfluorinated compounds.In all,the observation of complex network demonstrated a new and effective means for the study on the toxicity pathways of environmental pollutants.