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Comparative Study Of Early Toxic Effect In Rats Inhaled From Cigarette Smoke And Radon

Posted on:2010-10-30Degree:MasterType:Thesis
Country:ChinaCandidate:Y W WuFull Text:PDF
GTID:2144360275959262Subject:Health Toxicology
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Objective:To study the early toxic effect induced by cigarette smoke and radon in terms of DNA damage and chronic toxicity.Methods:(1)Male wistar rats were randomly divided into 3 groups with 6 rats in each group,i.e.,control group, low concentration(20%) and high concentration(60%) group.The rats were exposed to cigarette smoke twice a day, 30min each time,five day per week for a total of 45 weeks.(2)Male wistar rats were exposed to radon and its progeny in an environmentally controlled room with the low,middle and high dose group exposed up to a cumulative dose of 64,121 and 236WLM, respectively.(3) Blood and lung tisse were taken;and 24h urine sample were collected after the last exposure. 8-OHdG in lung tissue,peripheral blood lymphocytes and urine were detected by ELISA;T-AOC of lung tissue and serum were determined by ultraviolet spectrophotometer;RT-PCR was performed to detect the OGG1 and MTH1 mRNA level in lung tissue and peripheral blood lymphocytes.The fluorescence probe method was used to detected ROS in BALF cells.Pulmonary pathological changes were observed and bone marrow micronucleus were counted.Finally the heart,liver,spleen,kidney and testis were weighed and organ coefficient was calculated.Results:(1)In rats exposed to cigarette smoke,the 8-OHdG content of lung tissue,peripheral blood lymphocytes and urine increased with increased cigarette smoke concentration(P<0.01).The ROS level in BLAF cells increased (P<0.01)but the T-AOC level of lung tisse and peripheral blood lymphocytes decreased(P<0.05);The expression level of OGG1 and MTH1 decreased(P<0.05),and the expression level of MTH1 decreased with increased cigarette smoke(P<0.05).The body weight decreased(P<0.05),but bone marrow micronucleus level was found to be elevated(P<0.01).Emphysema and bronchitis were observed in lung tissue of the exposed groups,and collagen fibers in high concentration group increased significantly.(2)In rats exposed to radon, the 8-OHdG content of lung tissue,peripheral blood lymphocytes and urine increased,with no difference was found between groups, The ROS level in BLAF cells was found to be elevated (P<0.01),whereas the T-AOC levels in lung tissue and in peripheral blood lymphocytes was found to be decreased(P<0.05),The expression level of OGG1 in lung tissue and peripheral blood lymphocytes decreased(P<0.05).Compared with the control group, liver coefficient of high dose group increased but testis coefficient decreased(P<0.05). Bone marrow micronucleus level was found to be evaluated(P<0.01),and emphysema and bronchitis were observed in lung tissue of the exposed groups.Conclusion:(1)Cigarette smoke and radon induced DNA damage in lung tissue and peripheral blood lymphocytes.(2) DNA damage in peripheral blood lymphocytes could be used to reflect the lung injury induced by cigarette smoke and radon. (3)Urine 8-OHdG could be a useful marker to evaluate exposures to cigarette smoke and radon.
Keywords/Search Tags:Cigarette smoke, Radon, OGG1, MTH1, 8-OHdG
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