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Research On Influence Of Leukemia Susceptibility Factors Of Bone Marrow And Blood Tissue Of Mice Exposed To Formaldehyde

Posted on:2013-02-27Degree:MasterType:Thesis
Country:ChinaCandidate:J DuFull Text:PDF
GTID:2254330425994831Subject:Biochemistry and Molecular Biology
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With the rapid economic development, more and more formaldehyde (FA) is used in the construction and decoration materials. While the followed pollution problems can also not be ignored. It has become the major interior pollutant, which does serious harm to human health. A large number of researches showed that FA exposure can cause toxicity of respiratory, nervous, immune, genetic, reproductive system directly, even cancer. In recent decades, among diseases caused by formaldehyde, leukemia has been a hot and debate research. In2006, according to the "two key events" that FA can promote cell growth and form DPC, the International Institute for Cancer Research (IARC) classified FA as the group A1human carcinogen, and there is strong but not sufficient evidence that FA can cause leukemia.The view that FA can result in leukemia starts from epidemiology, and in recently years, a growing number of scholars mainly did the researches from the following two aspects using the molecular toxicology methods. Experts headed by Henry d’A mainly did their researches on whether FA can reach bone barrow and result in DNA-protein crosslinks (DPC) and the establishment of animal models of leukemia. While some experts believe some inhaled FA was hydrolyzed, and considerable part can be combined with certain molecules, such as nucleic acids, proteins, amines or amino acids. The combined FA can reach the target organs through blood circulatory, then release free FA and lead to toxicity. Both of them focused on "whether FA can result in long-range toxicity", that is whether FA can reach the target organs of leukemia-bone marrow and produce hematopoietic toxicity. Thus in the researches on whether FA can lead to leukemia, bone marrow and blood tissue are hubs.In order to investigate the toxicity of mice bone marrow and blood exposed to FA, in this study we used B/C male mice as experimental materials exposed to0,0.5,1.0,3.0mg/m3concentration of gaesous FA for a week,8h per day respectively. Then detecting the DNA-protein crosslinks and the expression of representative leukemia susceptibility factors-CYP1A1and GSTT1genes in the bone marrow cells and blood lymphocytes. The results showed that the DPC coefficients in the bone marrow cells and blood lymphocytes were on the rise with the concentration of FA. And compared with control, there was significant difference (P<0.01) at the lowest concentration of FA in the bone marrow. In addition, compared with control, there were different expression of CYP1A1and GSTT1genes in the Hela cells, bone marrow cells and blood lymphocytes. Therefore, FA can produce toxicity on bone marrow and blood system of mice. To compare with the toxicity of direct-contact cells exposed to FA, in this study Hela cells were collected as experimental materials to exposed to0,250,500,1000μmol/L of liquid FA respectively for1h. Then detecting the expression of CYP1A1and GSTT1genes. The results showed that FA can affect the expression of CYP1A1and GSTT1genes. It is demonstrated that FA can produce toxicity to both direct-contact cells and non-direct-contact cells. That is a question how does FA transfer to the non direct-contact cells? Stephen et al. found that the products of glutathione (GSH) and FA S-hydroxymethyl could help FA to achieve a long-range toxicity. In this study, Hela cells were collected as experimental materials exposed to250μmol/L GSH, FA, equal GSH and FA combined group and control group to investigate synergistic effect of GSH on the toxicity of FA cased by FA. The results show that compared with FA exposure group, the same concentration of GSH and formaldehyde combined group combined did significant harm to Hela cells. we speculated that FA can combine with GSH, the product S-hydroxymethyl glutathione may release free FA after reaching the target site and produce toxic. This provided a theoretical basis for FA and leukemia.
Keywords/Search Tags:Formaldehyde, Mice, Bone marrow and bolld system, Research
PDF Full Text Request
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