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.  If that damage goes unrepaired or is repaired incorrectly, permanent damage to tissues and organ systems can 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 activates genes controlling the cell cycle and DNA damage repair. Importantly, ERbeta is also a tumor suppressor that is commonly mutated in cancers. Regulation of ERbeta-mediated gene expression by BIO 300 (e.g., p53, p21, GADD45) dictates the extent, severity, and response to DNA damage from ionizing radiation, which together confer a radioresistant state to healthy cells. Because ERbeta targets genes that are 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.