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. 2019 Aug;16(3):396–414. doi: 10.20892/j.issn.2095-3941.2019.0097

2.

Estrogens (E<sub>1</sub>: estrone; E<sub>2</sub>: estradiol) are metabolized through two main pathways, forming 4- and 2-hydroxylated estrogens respectively, known as catechol estrogens (CEs). With further oxidation, CEs are converted to semiquinones (CE-SQs) and then to CE-quinones (CE-Qs), including E-3,4-Q and E-2,3-Q. CE-Q is a type of dangerous ROS, which attacks genomic DNA. This reaction results in the formation of depurinating adducts including 4-OHE-1-N3Ade, 4-OHE-1-N7Gua, and 2-OHE-6-N3Ade, leaving breaks in DNA. If lacking BRCA1, cells cannot repair the DNA damage. Accumulative DNA lesions lead to genomic instability and further breast cancer.

Estrogen oxidation-induced DNA damage and breast cancer.