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| TITLE: | Signal transduction pathways responsible for the oncostatic properties of melatonin | ||
| Principal Investigator |
Elizabeth Murphy, Ph.D. | Laboratory of Molecular Biophysics, NIEHS | |
| Health Relevance |
Cancer | ||
| Research Categories |
Cell Function | Cell Processes | Melatonin |
| FY95 Funds | DIR-8 $ 30,000 | Start Date 9/93 | End Date 9/95 |
| Rationale and Summary |
Exposure to low frequency electromagnetic fields (EMF) has been associated with several cancers. EMF exposure has also been shown to alter melatonin levels and to alter calcium homeostasis. Melatonin is oncostatic although the cellular mechanism of action is unknown. The focus of this research projects is to investigate whether melatonin induced ion signaling pathways (particularly involving calcium) are altered by EMF exposure. This proposal has three specific aims: 1) to determine whether melatonin alters intracellular calcium and/or pH; 2) to determine if melatonin alters the response of cells to hormones which alter calcium or pH, and 3) to determine if exposure to EMF alters melatonin induced changes in cell calcium or pH. We find that acute addition of melatonin does not alter intracellular ionized Calcium (Cai), but preliminary data suggest that chronic exposure to melatonin can attenuate growth hormone induced increases in Cai. We plan to investigate next whether exposure to EMF affects the ability of chronic melatonin treatment to attenuate the signaling pathways of growth hormones. | ||
| Experimental Design and Exposure Conditions |
BG1 cells were used in this study. To investigate whether acute addition of melatonin altered Cai, cells were treated with 10-5 to 10-9M concentrations of melatonin. Cai was measured using fluorescent microscopy in cells loaded with the fluorescent calcium indicator, fura-2. We have also investigated whether chronic exposure of melatonin alters the EGF induced increase in Cai. | ||
| Quality Assurance Measures |
In the upcoming year, we plan on using the FDA exposure chamber. We will utilize the expertise at this NIEHS funded exposure facility. | ||
| Results and Discussion |
Our data suggests that acute addition of melatonin does not alter Cai. BG1 cells were loaded with
fura-2AM and Cai was monitored using fluorescence microscopy. Acute addition of melatonin
(10-5 to 10-9M) did not alter Cai. We have begun to investigate whether chronic melatonin
exposure alters the response of BG1 cells to calcium activating hormones. Acute addition of EGF
results in an increase in Cai. We are currently investigating whether pretreatment of cells with
melatonin attenuates the EGF induced increase in Cai. Preliminary studies have also shown that
DMSO can induce proliferation in BG1 cells, and melatonin can block this increase in
proliferation. After we have documented the acute effect of melatonin as well as its ability to alter
the response of other growth hormones, such as EGF, we will then investigate whether these
responses are altered by EMF exposure.
These data will be used for a collaborative project between NIOSH, the Laboratory of Molecular Biophysics, NIEHS, and the Laboratory of Molecular Carcinogenesis to assess the effect of EMF on calcium homeostasis and cell cycle regulation. |
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| Recent Publications |
None | ||