Regulatory heme and trichloroethylene intoxication: A possible explanation of the case of "A Civil Action".

Environ Health Prev Med

Laboratory of Environmental Biology, Hokkaido University School of Medicine, North 15, West 7, Kita-ku, 060-8638, Supporo, Japan.

Published: July 2002

In 1998, a amovie 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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2723491PMC
http://dx.doi.org/10.1265/ehpm.2002.103DOI Listing

Publication Analysis

Top Keywords

regulatory heme
12
heme trichloroethylene
8
trichloroethylene intoxication
8
civil action"
8
cases trichloroethylene
8
trichloroethylene pollution
8
trichloroethylene
6
leukemia
5
heme
5
intoxication explanation
4

Similar Publications

Deciphering the impact of NOS-derived NO on nitrogen metabolism and carbon flux in the heterocytous cyanobacterium Aphanizomenon flos-aquae 2012/KM1/D3.

Plant Physiol Biochem

January 2025

Laboratory of Microbial Genetics, Department of Botany, Institute of Science, Banaras Hindu University, Varanasi, 221005, India. Electronic address:

Nitric oxide synthases (NOSs) are heme-based monooxygenases that catalyze the NADPH-dependent oxidation of L-arginine to produce NO and L-citrulline. Over the past five years, the identification and characterization of NOS homologs in cyanobacteria have significantly advanced our understanding of these enzymes. However, the precise mechanisms through which NOS-derived NO influences nitrogen metabolism remain incompletely elucidated.

View Article and Find Full Text PDF

Regulatory and retrograde signaling networks in the chlorophyll biosynthetic pathway.

J Integr Plant Biol

January 2025

Key Laboratory of Photobiology, Institute of Botany, the Chinese Academy of Sciences, Beijing, 100093, China.

Plants, algae and photosynthetic bacteria convert light into chemical energy by means of photosynthesis, thus providing food and energy for most organisms on Earth. Photosynthetic pigments, including chlorophylls (Chls) and carotenoids, are essential components that absorb the light energy necessary to drive electron transport in photosynthesis. The biosynthesis of Chl shares several steps in common with the biosynthesis of other tetrapyrroles, including siroheme, heme and phycobilins.

View Article and Find Full Text PDF

Insights into the diverse roles of the terminal oxidases in Burkholderia cenocepacia H111.

Sci Rep

January 2025

Department of Plant and Microbial Biology, University of Zurich, Zollikerstrasse 107, Zürich, 8008, Switzerland.

Burkholderia cenocepacia H111 is an obligate aerobic bacterium which has been isolated from a cystic fibrosis (CF) patient. In CF lungs the environment is considered micro-oxic or even oxygen-depleted due to bacterial activities and limited oxygen diffusion in the mucus layer. To adapt to low oxygen concentrations, bacteria possess multiple terminal oxidases.

View Article and Find Full Text PDF

Osteocytes are the main cells in mineralized bone tissue. Elevated osteocyte apoptosis has been observed in lytic bone lesions of patients with multiple myeloma. However, their precise contribution to bone metastasis remains unclear.

View Article and Find Full Text PDF

Ovarian ischemia is a pathological condition that usually occurs due to ovarian torsion, resulting in the interruption of blood supply to the ovaries and oxygen deficiency. Silymarin (SLM) is a flavonoid complex of plant origin with pharmacological properties such as antioxidant, anti-inflammatory, and antiapoptotic effects. In this study, we investigated the effects of SLM through different pathways in rats subjected to experimental ovarian ischemia/reperfusion (I/R).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!