Selenium Potentiates Chemotherapeutic Selectivity: Improving Efficacy and Reducing Toxicity
Abstract
In mice, selenium in the form of seleno-L-methionine was reported to have two effects 1) to enhance efficacy of cancer therapeutics against cancer cells; and 2) to protect bone marrow and gut epithelium from dose-limiting toxicity. We are exploring the mechanism whereby selenium can have differential effects on cancer cells versus normal cells. A key genetic alteration in cancer is p53 mutation. About 70% of all human cancers are mutant i.e. defective in p53, while bone marrow and other normal tissues are functional for p53. P53 is known to protect normal cells by a DNA repair mechanism. Cancer cells lack the DNA repair mechanism and are predicted to be sensitive to chemotherapy. A DNA repair protein that is controlled by p53 is Xpc. Thus, wildtype, p53-/-, or xpc-/- mice were used to test the hypothesis that 1) selenium evoked a DNA repair and protective response in wildtype cells including bone marrow; and 2) DNA repair was defective in cells deleted for p53 or xpc genes and these cells including cancer cells would not be protected.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2008
- Accession Number
- ADA489923
Entities
People
- Joshua L. Fischer
Organizations
- Indiana University