DNA Damage In Different Tissues From Rat Induced By NO₂Inhalation

As a common atmospheric pollutant, the emission of NO2is increasing in recent years. Epidemiological studies show that the incidence and mortality of respiratory diseases, cardiovascular disease, and local ischemic heart disease increased with the elevated level of NO2in the atmosphere. Toxicology studies have shown that different concentrations of NO2can result damage in the lung, spleen, kidney, liver and other organs of animal, leading to a variety of respiratory diseases and even lead to the occurrence of lung cancer, hematological changes and the decline of immune function. At present, the researche of NO2are mainly focus on the inflammatory response and oxidative stress, DNA damage caused by NO2and its molecular mechanism study rarely reported.In order to investigate the DNA damage of organisms resulted by NO2and its molecular mechanism, to provide basic data and some theoretical guidance to the clinical treatment of human health protection of NO2pollution incident, this paper do a depth research of DNA damage caused by NO2in rat liver, kidney, spleen, heart cells. Firstly, rats were exposed into different concentrations of NO2(0,5,10,20mg/m3),6h a day, continuous7d; And then, to judge the extent of DNA damage of different organs and to explore the dose-effect relationship, the degree of DNA-protein crosslink (DPC) and DNA fragmentation in various organs of rats were measured with KC1-SDS precipitation method and Single cell gel electrophoresis respectively. The experimental results are as follows:1. After inhalation exposure to different concentrations (0,5,10,20mg/m3) of NO2, the DPC coefficient in different organs (liver, kidney, spleen and heart) of Rats are affected, the DPC coefficient increased with the increase of NO2concentrations, both showing a positive correlation. The growth of DPC coefficient in Liver is largest in different concentrations of NO2.2. After inhalation exposure to different concentrations (0,5,10,20mg/ml) of NO2, the Olive tail moment(OTM), Tail moment(TM), Tail length(TL), Tail DNA percentage content(TDNA) and the Rate of comet cells in different organs (liver, kidney and spleen) of Rats are affected. Compared with the control group, the indexes of exposure groups increased with the elevated of NO2concentration, both showing a positive correlation. when NO2concentration is20mg/m3,the Growth order of the above five indexes is that:spleen>liver>kidney; except TM, when NO2concentration is10mg/m3, the Growth order of the Other indexes is that:spleen>liver>kidney; when NO2concentration is5mg/m3, the Growth order of TM, TL and the Rate of comet cells is that:liver>kidney>spleen, and the Growth order of the other two indexes is that:liver>spleen>kidney.In summary, rats DNA is damaged in some degree after inhalation exposure by NO2. Its possible mechanism is showed as follow:NO2in vivo of rats can generate reactive oxygen species, with the increase of ROS formation, the body’s antioxidant system is damaged, and the generated ROS attack DNA resulting DNA single-stranded and double-stranded breaks happened. After the DNA was broken, DNA fragmentation can combine with Protein, as a result, DPC is formation; On the other hand, Lipid peroxidation products which formation by free radicals attack polyunsaturated fatty acids can also Promoted the formation of DPC.