A Primary Study On Genotoxicity And Pathogenesis Of Asthma Induced By DEHP

Since 21st century,Chinese phthalate esters industries are developing rapidly,and the current annual output has exceeded that of Japan,only after the United States,takes the second place in the world.Moreover Chinese phthalate esters consumption has taken the place of the United States,becomes the largest consumption country in the world. The Chinese residents' body load of phthalate esters is growing rapidly.Previous studies have shown that the phthalate esters had toxic effects on the body through various ways. Di-(2-ethylhexyl)phthalate(DEHP)is the most widely used of a phthalate esters,in the plastic industry is very important plasticizer.Now the research of the toxicity of DEHP is a hot and difficult spot in the field of hygienical.This research is to explore the DEHP-induced asthma and pathogenesis of asthma and the role of genotoxicity,which is of great significance to understand the toxicity of DEHP.In this study,Wistar rats were used to establish the DEHP-induced asthma model exposed by gastric gavage.As regards, the AHR testing,lung histology and cytokines profiles were studied to discuss the DEHP-induced asthma pathogenesis,at the same time,SDS - KCl assay was used to tested on rat liver cells of genetic toxicity.The results are as follows:1.DNA-protein crosslinks induced by DEI-IPThere are a certain amount of DNA-protein crosslinks(DPC)in normal cells,which has normal connection between DNA and nuclein.Therefore,DPC is important to support the cell growth.Excessive DPC can be induced by environmental pollutants and carcinogen.Compared with other types of DNA damage,DPC is hard to be repaired,and DPC only can be in the single strand DNA,which shows that DPC can be induced during replication and transcription.So DPC has serious influence to DNA configuration and functions and can cause some important genes loss(such as tumor suppressor gene). Excessive DPC is a pathological phenomenon and a serious genetic damage in DNA.In this study,rat liver cells were used to detect the DEHP-induced DPC by the SDS-KCl assay.The results showed that a higher concentration of DEHP can induce DPC in rat liver cells.2.Potential role of DEHP in the pathogenesis of asthmaAsthma is a chronic respiratory disease.WHO defined asthma as a lifelong disease, asthma caused tremendous financial burden to the world.In recent 40 years,asthmatic morbidity and mortality increased continuously all the world.The gaseous pollutants were suspected to be a major reason,but the molecular mechanism of allergic asthma is not clear.So the molecular mechanisms of asthma are important to be revealed for its significance to the field of scientific research and the society.Epidemiological studies have suggested that DEHP has been associated with the development of asthma or asthma symptoms.However,Butala's study has show that DEHP was not allergen,there was no specific anti-DEHP-IgE formed after DEHP treatment in the animal.This has led to a conception that DEHP may cause asthma via a non-IgE-mediated mechanism.According to our previous study,we proposed "atopy stressor" and "acquired atopy" hypothesis,we assumed the DEHP played as an "atopy stressor" role in asthma,it can increase the body's total IgE level so called "acquired atopy".It can induced asthma even faced a lower levels of allergens.This study showed that the rats exposed to DEHP by gavage alone will not trigger asthma,only contact with allergens(e.g.OVA)at the same time can induce asthma.