Analogs of Estrogen Metabolites as Probes of Estrogen-Induced Tumorigenesis.
Abstract
2- AND 4-Hydroxyalkyl estradiols were synthesized as biochemically stable Catechol estrogen mimics. These analogs were used as chemical probes to evaluate the proposed involvement of catechol estrogens in the initiation of breast cancer. Potentiometric studies performed in PBS buffer at pH 7.4 showed that catechol estrogens were able to undergo redox cycling whereas the Hydroxyalkyl estradiols unable to redox cycle. In agreement with potentiometric studies we have shown that Catechol estrogens are able to induce 8-oxo-dG formation in calf thymus DNA. Our studies have shown that presence of Cu(II) causes a significant increase in DNA damage induced by Catechol estrogens. The Hydroxyalkyl analogs failed to induce 8-oxo-dG formation even in presence of Cu(II). It is important to note that the Catechol estrogens can produce DNA damage at concentrations much higher than their normal physiological levels. Estrogen A-ring fused heterocycles were synthesized as potential inhibitors of Estrogen hydroxylase, the enzyme responsible for producing Catechol estrogens in the body. 2-Methoxymethyl estradiol was identified as an inhibitor of tubulin polymerization.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1998
- Accession Number
- ADA354648
Entities
People
- Abhijit S. Bbat
Organizations
- Ohio State University