| Formaldsehyde (FA) is a major chemical pollutants. In our country there are more than 2 million U.S. workers occupationally exposed. Substantially more people are exposed to formaldehyde environmentally, as it is generated by automobile engines, is a component of tobacco smoke and is released from household products, including furniture, particleboard, plywood, and carpeting. The International Agency for Research on Cancer (IARC) recently classified FA as a human carcinogen that causes nasopharyngeal cancer and also concluded that there is "strong but not sufficient evidence for a causal association between leukemia and occupational exposure to formaldehyde". The biological plausibility of this observed association is discussed and potential mechanisms proposed.Some experts believe FA can cause leukemia, but still now the mechanism is not clear. They speculated that FA may cause leukemia by three mechanisms. One is traditional model which suggest FA can damage targeting hematopoietic stem cells in bone marrow directly, the other two are alternate mode which suggest FA can damage targeting stem,progenitor cells in circulating peripheral blood and primitive pluripotent cells in nasal or oral passages firstly, then the damaged cells circulated with blood and travel to bone marrow and become lekemic stem cells.However, some authors have argued that it is biologically implausible for FA to cause leukemia. They believe FA is highly reactive and easily degradable by formaldehyde dehydrogenase after entering the body, so it is unlikely to reach the bone marrow and cause toxicity. The debate focused on distance-site toxicity, whether the toxicity of FA can reach the bone marrow.To test the exist of distance-site toxicity, we choose KunMing male mice as experimental animal and exposed them to different concentration of formaldehyde. We carried out the study from three levels to research the toxicity of FA and its possible mechanism of long-range toxicity. First of all, the study was carried out at the cellular level by measuring micronuclei of liver cells and peripheral blood lymphocytes cells to detect the damage to the cells in blood and organs. The results showed that micronuclei rate of peripheral blood lymphocytes exposed to FA has highly significant difference (P <0.01) to control group. The result of liver cells micronuclei showed that micronuclei rate of liver cells rise with the FA dose increasing. Both of the results told us FA exposure can cause heritage damage to liver cells and peripheral blood lymphocytes cells. Secondly, the study was carried out at the molecular level (DNA level) by detecting RAPD changes of liver cells and bone marrow cells to test whether the toxicity of formaldehyde can reach the liver and bone marrow cavity and impact on genetic material DNA. The result showed that the change of DNA polymorphism could be found both in liver cells and bone marrow cells and the change level rise with the dose of FA increased. It indicated that formaldehyde reached the liver and bone marrow cavity and caused damage to their genetic material DNA. Thirdly, the study was carried out at the transcriptional level (RNA level). Detect the change of transcription factor HOXB4 which can regulate hematopoietic levels. The result of RT-PCR showed that gene expression quantity of HOXB4 reduced with formaldehyde dose increased. So we may forecast that formaldehyde exposure could lead to the increased risk of leukemia. |
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