Heptachlor epoxide induces a non-capacitative type of Ca2+ entry and immediate early gene expression in mouse hepatoma cells.

Abstract

The effects of the organochlorine (OC) liver tumor promoter heptachlor epoxide (HE) and a related non-tumor promoting OC, delta-hexachlorocyclohexane (delta-HCH), on the dynamics of intracellular calcium (Ca2+) were investigated in mouse 1c1c7 hepatoma cells. HE induced a non-capacitative, Ca2+ entry-like phenomenon, which was transient and concentration-dependent with 10 and 50 microM HE. The plasma membrane Ca2+ channel blocker SKF-96365 antagonized this HE-induced Ca2+ entry. delta-HCH failed to induce Ca2+ entry, rather it antagonized the HE-induced Ca2+ entry. Both HE and delta-HCH induced Ca2+ release from endoplasmic reticulum (ER) at treatment concentrations as low as 10 microM; at 50 microM, the former induced 5x as much Ca2+ release as the latter. The HE-induced Ca2+ release from the ER was antagonized using the IP3 receptor/channel blocker xestospongin C, suggesting that HE induces ER Ca2+ release through the IP3 receptor/channel pore. These results show that the effect of HE on cellular Ca2+ mimics that of mitogens such as epidermal and hepatocyte growth factors. They also provide insight into the similarities and differences between tumorigenic and non-tumorigenic OCs, in terms of the mechanisms and the extent of the [Ca2+]i increased by these agents.

• Authors: Mark E Hansen, Isaac N Pessah, Fumio Matsumura
• Journal: Toxicology (Toxicology) Vol. 220 Issue 2-3 Pg. 218-31 (Mar 15 2006) ISSN: 0300-483X [Print] Ireland
• PMID: 16469423 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channel Blockers
• Calcium Channels
• Enzyme Inhibitors
• Imidazoles
• Insecticides
• Macrocyclic Compounds
• Oxazoles
• Transcription Factor AP-1
• xestospongin A
• Heptachlor Epoxide
• delta-hexachlorocyclohexane
• Hexachlorocyclohexane
• 1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Calcium Channel Blockers (pharmacology)
• Calcium Channels (metabolism)
• Calcium Signaling (drug effects)
• Carcinoma, Hepatocellular
• Cell Line, Tumor
• Endoplasmic Reticulum (metabolism)
• Enzyme Inhibitors (pharmacology)
• Gene Expression
• Heptachlor Epoxide (toxicity)
• Hexachlorocyclohexane (toxicity)
• Imidazoles (pharmacology)
• Insecticides (toxicity)
• Macrocyclic Compounds
• Mice
• Oxazoles (pharmacology)
• Transcription Factor AP-1 (metabolism)