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Preliminary Studies On The Genotoxicity And The Lymphocyte Injury Induced By Pesticide Rotenone In Vivo And In Vitro

Posted on:2006-04-03Degree:MasterType:Thesis
Country:ChinaCandidate:X YangFull Text:PDF
GTID:2144360155473853Subject:Military Preventive Medicine
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Rotenone, a broad spectrum biopesticide from Derris elliptica, has been widely used in agriculture because of its characteristics of high efficiency and non-pesticide resistance. As the top one of the intensive pesticides to be developed in the new century, rotenone is getting more and more attention on its pollution to the earth and the harm to the human. Preliminary results from epidemiological investigation indicated a relationship between rotenone and Parkinson's disease (PD). A neurodegenerative change in central system was also demonstrated by rotenone perfuse in animal models. Therefore, rotenone exposure is regarded as one of the reasons of the PD. However, no extensive study was reported on the systemic effect induced by rotenone. The present study was designed to investigate the genotoxic activity of rotenone on three genetic endpoints, reversible mutation, chromosomal aberration (CA) and micronuclei (MN). At the same time we investigated rotenone-induced structural and functional changes in lymphocytes and its mechanism in vivo and in vitro. Our results indicated that rotenone at the concentrations used doesn't increase the frequency of reversible mutation, and the same in chromosomal aberration and micronuclei. Immunity function of the rats intoxicated by rotenone is obviously severely suppressed, and the humoral immunity (T-lymphocytes) is more sensitive than cellular immunity (B-lymphocytes). It has been charactered that changes took place early and resumed quickly, and IL-2 and IL-6 have done the same. We found the typical DNA damage (DNA ladder) after lymphocytes intoxication in vitro about 4 hours by rotenone in the agarose gel electrophoresis. DNA smear, a symbol of cell death, was found after the lymphocytes intoxication in vitro about 12 hours. In the study on genotoxicity, the results indicate that rotenone doesn't increase the frequency of mutations at the concentrations used. In the part of the study on immune system, the results indicated that immune system of the rats intoxicated by rotenone is obviously dysfunctional, and the humoral immunity is more sensitive than cellular immunity. It is charactered that changes took place early and resumed quickly. IL-2 and IL-6 could be regarded as two sensitive parameters to evaluate cytotoxicity and early diagnosis in the intoxication. By the results of the agarose gel electrophoresis, it suggest that the mechanism of toxicity could be as follows: Cell death induced by DNA damages causes a decrease in the number of lymphocytes. Apoptosis mediates the earlier period of cell damage. In the later period, necrosis is the symbol of cell death. These results suggest that rotenone could produce immune system dysfunction in vivo.
Keywords/Search Tags:rotenone, genotoxicity, reversible mutation, chromosomal aberration, micronuclei, spleen, lymphocyte, MTT, IL-2, IL-6, DNA damage, apoptosis, necrosis
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