BIO 300 - Mechanism of Action
Understanding Radiation Toxicity – An Issue of DNA Damage
Humans are exposed to ionizing radiation through several means. Cancer patients are intentionally exposed to radiation in an effort to kill rapidly dividing tumor cells. Other sources include accidental or intentional exposure from radiological or nuclear events. The consequences of radiation exposure range from mild and reversible tissue damage, to long-term tissue remodeling and even to death in cases of high exposure.
Ionizing radiation is harmful because it indiscriminately ionizes anything in its path. The human body is ~90% water, ionization of these water molecules generates reactive oxygen species, which can damage cellular DNA. Radiation exposure can also trigger a chronic inflammatory response. If DNA damage goes unrepaired or is repaired incorrectly, and inflammation isn’t controlled, then permanent damage to tissues and organ systems will lead to long term adverse health effects.
BIO 300 Protects the Health of Cellular DNA
BIO 300 acts as a highly-selective agonist for estrogen receptor-beta (ERbeta), a transcription factor found throughout the body that regulates genes controlling the cell cycle, DNA damage repair and inflammation. Importantly, ERbeta is also a tumor suppressor and higher ERbeta expression is prognostic for better patient outcomes following solid tumor radiotherapy. Regulation of ERbeta-mediated gene expression (e.g., p53, p21, GADD45A) or gene suppression (e.g., NF-kb, COX2, TNFa) by BIO 300 dictates the extent, severity, and response to DNA damage from ionizing radiation, which together confer a radioresistant state to healthy cells. Because ERbeta, along with its target genes, is commonly mutated in cancer, the radioprotective properties of BIO 300 do not extend to cancer cells. Through this mechanism, BIO 300 prevents damage to normal tissues in patients undergoing radiation therapy for solid tumors, while still allowing the radiation to kill the tumor.