Regulatory Heme and Trichloroethylene Intoxication : A Possible Explanation of the Case of "A Civil Action"

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概要

• 論文の詳細を見る

• In 1998, a movie entitled "A Civil Action" was released. The movie described the Woburn case, begun in 1982 and concluded in 1990, one of the most famous cases of trichloroethylene pollution. In a small town near Boston, twelve children died of leukemia, which seemed attributable to trichloroethylene contamination of the drinking water. The victims, however, could not win the case, since evidence that the identified chemicals could cause leukemia and other human illnesses was rather sketchy. There have been many cases of trichloroethylene pollution in industrial nations including Japan, therefore, we reconsidered the missing link. Our conclusion is that the disease occurred not by a direct effect of the chemical hazard on biological macromolecules but by an indirect effect through the physiological system such as signal transduction and transcriptional regulation. In 1984, we reported a marked reduction in the regulatory heme pool by trichloroethylene exposure, however, the biological significance was not well understood. Recently, we found that the DNA binding activity of Bach1, a negative regulator of genes, is controlled by heme, the regulation of which seems to explain how leukemia develops. The heterodimer of Bach1 with MafK recognizes Maf recognition elements (MAREs) competing with the erythroid type positive regulator, a complex of NF-E2 with MafK. Bach1/MafK occupies MAREs under lower heme conditions, whereas MAREs are open to NF-E2/MafK along with increasing heme concentration. Since the NF-E2/MafK function is closely related to normal erythroid differentiation, of which disorders such as sideroblastic anemia are often related to neoplasia ; i.e., a clonal disorder that can progress to leukemia. Thus, a marked decline in regulatory heme by trichloroethylene intoxication could be one of the pathways to leukemia.

• 日本衛生学会の論文

著者

• Fujita Hiroki

  Division Of Geriatric Medicine Akita University Hospital

• Ogawa Kazuhiro

  Laboratory Of Environmental Biology Hokkaido University School Of Medicine

• FUJITA Hiroyoshi

  Laboratory of Environmental Biology, Hokkaido University School of Medicine

• NISHITANI Chiaki

  Laboratory of Environmental Biology, Hokkaido University School of Medicine

• Nishitani Chiaki

  Laboratory Of Environmental Biology Hokkaido University School Of Medicine

• Fujita Hiroyoshi

  Laboratory Of Environmental Biology Hokkaido University School Of Medicine

• Fujita Hiroyoshi

  Laboratory Of Environmental Biology Department Of Preventive Medicine Hokkaido University

関連論文

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• Determination of Optimal Protein Contents for a Protein Restriction Diet in Type 2 Diabetic Patients with Microalbuminuria
• Regulatory Heme and Trichloroethylene Intoxication : A Possible Explanation of the Case of "A Civil Action"
• Heme-Regulated Transcription Factor Bach1
• Lead, Chemical Porphyria, and Heme as a Biological Mediator
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