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Effects of organic and inorganic selenium compounds on rat mammary tumor cells
Z Ronai1, J K Tillotson, F Traganos
1American Health Foundation, Valhalla, N.Y. 10595, USA.
Abstract:
To explore cellular effects of potent organoselenium chemopreventive agents we have used a rat mammary tumor cell line. We demonstrate that 1,4-phenylenebis(methylene) selenocyanate (p-XSC) at a dose of 5 microM is a more potent inhibitor of DNA, RNA and protein synthesis as well as of mitochondrial transmembrane potential than its chemopreventive counterparts benzyl selenocyanate (BSC) and sodium selenite. These differences were also reflected in reduced growth rate by 24 and 48 hr. Cell-cycle and cell-morphology analysis revealed that higher doses of p-XSC (10 microM) caused DNA fragmentation which was accompanied with partial loss of nuclear stainability, whereas BSC caused a noticeable change in cell-cycle distribution and extensive micronucleation. Overall, our results point to cellular targets of selenium compounds which may mediate their chemopreventive activities in mammary tissues.
Insights
1,4-phenylenebis(methylene) selenocyanate (p-XSC) is a potent organoselenium compound that inhibits DNA, RNA, and protein synthesis in rat mammary tumor cells. It shows greater efficacy than benzyl selenocyanate (BSC) and sodium selenite in cellular chemoprevention studies.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Organoselenium compounds are recognized for their chemopreventive potential.
- Understanding the cellular mechanisms of these agents is crucial for developing effective cancer prevention strategies.
Purpose of the Study:
- To compare the cellular effects of 1,4-phenylenebis(methylene) selenocyanate (p-XSC) with other organoselenium compounds.
- To investigate the impact of p-XSC on DNA, RNA, protein synthesis, and mitochondrial function in a rat mammary tumor cell line.
Main Methods:
- Utilized a rat mammary tumor cell line for in vitro studies.
- Assessed inhibition of DNA, RNA, and protein synthesis.
- Measured mitochondrial transmembrane potential.
- Performed cell-cycle and cell-morphology analyses.
Main Results:
- p-XSC (5 microM) significantly inhibited DNA, RNA, and protein synthesis more potently than benzyl selenocyanate (BSC) and sodium selenite.
- p-XSC also reduced mitochondrial transmembrane potential and growth rate.
- Higher doses of p-XSC (10 microM) induced DNA fragmentation and nuclear changes.
- BSC treatment resulted in altered cell-cycle distribution and micronucleation.
Conclusions:
- p-XSC exhibits superior cellular inhibitory effects compared to BSC and sodium selenite.
- These findings suggest specific cellular targets for selenium compounds in mammary tissue chemoprevention.
- The study provides insights into the mechanisms underlying organoselenium chemoprevention.