Enhancing Radon
Risk Management: Integratingg Genetic Vulnerabilities and Environmental Co-exposures into the AOP Framework
By Klea Hondro, April 30, 2025
Radon is an invisible, odorlesss, and naturally occurring radioactive gas produced from the decay of uranium and thorium in soil and rocks. It is a well-known health hazard and a leading cause of lung cancer worldwide, second only to smoking. While the health impacts of radon are well established through decades of epidemiological and toxicological research
, connecting the cellular-level biological changes to broader health outcomes remains a crucial scientific frontier.
To bridge this gap, researchers are applying the
Adverse Outcome Pathway( AOP) framework. AOPs help trace the progression from molecular events, like
DNA damage, through cellular and tissue-level changes, ultimately resulting in disease outcomes such as lung cancer. This structured approach offers a way to unify molecular, experimental, and population-level data into a coherent model that can better inform public health decisions.
Unpacking the Science with AOPs To bridge the gap between molecular science and public health, toxicologistss use Adverse
Outcome
Pathways( AOPs). These frameworks trace the progression from a molecular initiating event( MIE
) to a final health outcome. For radon, the MIE is alpha particle-induced DNA damage. This is followed by key events( KEs):
1. Oxidative stress from reactive oxygen species, 2. Impaired DNA repair and mutations
, and 3. Chronic inflammation creates a tumor-promoting environment.
The final adverse outcome is lung cancer, particularly non-small cell lung cancer( NSCLC). The OECD has endorsed this AOP for radon, validating it for regulatory use. Yet, the current model assumes all people respond the same. That’ s where the next frontier of radon science begins.