Chemopreventive Effects of ROS Targeting in a Murine Model of BRCA1-Deficient Breast Cancer.

ABSTRACT: There remains great interest in practical strategies to limit the elevated risks of familial breast and ovarian cancers driven by BRCA1 mutation. Here, we report that limiting the production of reactive oxygen species (ROS) is sufficient to reduce DNA lesions and delay tumorigenesis in a murine model of BRCA1-deficient breast cancer. We documented a large amount of endogenous estrogen oxidative metabolites in the mammary gland of the model, which induced DNA adducts and apurinic/apyrimidinic sites associated with DNA double-strand breaks and genomic instability. Repressing estrogen oxidation via antioxidant treatments reduced oxidative DNA lesions and delayed the onset of mammary tumors. Overall our work suggests an answer to the long-standing question of why germline BRCA1 mutations cause

SUBMITTER: Li M 

PROVIDER: S-EPMC5596625 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature