Adverse outcome pathways for ionizing radiation and breast cancer involve direct and indirect DNA damage, oxidative stress, inflammation, genomic instability, and interaction with hormonal regulation of the breast.

Adverse outcome pathways for ionizing radiation and breast cancer involve direct and indirect DNA damage, oxidative stress, inflammation, genomic instability, and interaction with hormonal regulation of the breast. Arch Toxicol. 2020 May 13;: Authors: Helm JS, Rudel RA Abstract Knowledge about established breast carcinogens can support improved and modernized toxicological testing methods by identifying key mechanistic events. Ionizing radiation (IR) increases the risk of breast cancer, especially for women and for exposure at younger ages, and evidence overall supports a linear dose-response relationship. We used the Adverse Outcome Pathway (AOP) framework to outline and evaluate the evidence linking ionizing radiation with breast cancer from molecular initiating events to the adverse outcome through intermediate key events, creating a qualitative AOP. We identified key events based on review articles, searched PubMed for recent literature on key events and IR, and identified additional papers using references. We manually curated publications and evaluated data quality. Ionizing radiation directly and indirectly causes DNA damage and increases production of reactive oxygen and nitrogen species (RONS). RONS lead to DNA damage and epigenetic changes leading to mutations and genomic instability (GI). Proliferation amplifies the effects of DNA damage and mutations leading to the AO of breast cancer. Separately, RONS and DNA damage als...
Source: Archives of Toxicology - Category: Toxicology Authors: Tags: Arch Toxicol Source Type: research