Sustained Increase in Intracellular Free Calcium and Activation of Cyclooxygenase-2 Expression in Mouse Hepatoma Cells Treated with Dioxin
2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) is a non-genotoxic environmental pollutant that causes multiple adverse effects in experimental animals and in humans. We show here that TCDD treatment of mouse hepatoma cells causes a rapid mobilization of intracellular calcium both in wild type Hepa-1 ce...
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Published in | Biochemical pharmacology Vol. 54; no. 12; pp. 1287 - 1296 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
New York, NY
Elsevier Inc
15.12.1997
Elsevier Science |
Subjects | |
Online Access | Get full text |
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Summary: | 2,3,7,8-tetrachlorodibenzo-
p-dioxin (TCDD) is a non-genotoxic environmental pollutant that causes multiple adverse effects in experimental animals and in humans. We show here that TCDD treatment of mouse hepatoma cells causes a rapid mobilization of intracellular calcium both in wild type Hepa-1 cells and in its
c2 variant, a cell line that has highly reduced levels of functional aromatic hydrocarbon (Ah) receptor (AHR). In wild type cells, but not in the
c2 variant, TCDD treatment leads to a sustained elevation of cytosolic free calcium. TCDD also induces elevated levels of cyclooxygenase-2 (COX-2) mRNA in wild type and in
c37, a CYP1A1-deficient cell line, but not in
c2 cells. Induction of
Cox-2 is in fact dependent on the presence of a functional Ah receptor, since it can be blocked by antisense oligonucleotides to Ah receptor mRNA. Most likely as a consequence of Cox-2 induction, we find a significant increase in the level of 12-hydroxyheptadecatrienoic acid (12-HHT) secreted from TCDD-treated Hepa-1 cells. In addition, we observe elevated levels of 6-keto prostaglandin F
1α in
c2 cells and high levels of secreted prostaglandin F
2α in
c2,
c37 and
c4, the variant cell line lacking aromatic hydrocarbon nuclear translocator protein. These data suggest that Cox-2 activation by TCDD leads to the release of prostaglandins, eicosanoids and other mediators which may have an important role in the biological and toxic effects of TCDD. |
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ISSN: | 0006-2952 1873-2968 |
DOI: | 10.1016/S0006-2952(97)00417-6 |