Figure 4.

Metabolic byproducts of 17β-estradiol (E2) exerting genotoxic effects. 17β-estradiol (E2) is converted by cytochrome P450 (CYP)-dependent hydroxylation to 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2). CYP enzymes or peroxidases convert these substrates into semiquinones (SQ), which may react with O₂ to generate superoxide radicals (OH•) that are highly reactive and induces proteins and lipids oxidation, DNA bases oxidation, and single-strand breaks (SSB). SQ can be also converted to quinones (Q) that can covalently bind DNA thus inducing DNA and/or chromosomal damage. Overall, these events cause genome instability and cell transformation. For details, see the text.