What is the Origin of Genotoxic Estrogen Metabolites?

These metabolites are formed via the hydroxylation of parent estrogens by Cytochrome P450 enzymes, which creates catechol estrogen intermediates such as 4-hydroxyestrone or 16-hydroxyestrone. The term 'genotoxic' denotes the compound's ability to cause damage to the cell's genome.

What is the Mechanism of Genotoxic Estrogen Metabolites?

The mechanism of genotoxicity centers on the further oxidation of certain hydroxylated estrogens, particularly 4-hydroxy-estrone, into highly reactive quinone intermediates. These quinones are electrophilic and readily bind covalently to purine and pyrimidine bases in DNA, forming stable DNA adducts that interfere with normal DNA replication and repair processes, thereby overwhelming cellular defenses and promoting carcinogenesis.

Genotoxic Estrogen Metabolites ∞ Area

Genotoxic Estrogen Metabolites

Meaning

Genotoxic Estrogen Metabolites are specific, chemically reactive compounds produced during the Phase I metabolic breakdown of endogenous estrogens that possess the inherent capacity to directly damage cellular DNA. This damage, if unrepaired, can lead to genetic mutations and is hypothesized to be a critical step in the initiation of hormone-sensitive cancers.