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Adduction of catechol estrogens to nucleosides
Isabelle Jouanin1, Laurent Debrauwer, Gwénola Fauglas
1Laboratoire des Xénobiotiques, INRA, 180 Chemin de Tournefeuille, BP 3, 31931 Toulouse Cedex 09, France.
Steroids
|November 21, 2002
Summary
Catechol estrogens (CE) can form adducts with DNA building blocks, deoxyadenosine and deoxyguanosine. These reactions yield stable DNA adducts and potential purine loss, impacting DNA integrity.
Area of Science:
- Environmental Chemistry
- Molecular Biology
- Organic Chemistry
Background:
- Catechol estrogens (CE) are metabolites of estrogen hormones.
- CE can undergo oxidation to reactive quinones.
- DNA damage is a significant factor in various diseases.
Purpose of the Study:
- To investigate the adduction of deoxynucleosides to catechol estrogens.
- To characterize the resulting adducts and understand their formation mechanisms.
- To assess the potential for DNA damage and modification.
Main Methods:
- One-pot synthesis involving catechol oxidation and Michael-type addition.
- High-performance liquid chromatography (HPLC) separation.
- Liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS(n)) for detection and structural characterization.
Main Results:
- Deoxynucleosides (deoxyadenosine, deoxyguanosine, deoxycytidine, 5-methyldeoxycytidine) were successfully adducted with CE.
- Pyrimidine deoxynucleosides formed stable CE-DNA adducts.
- Purine deoxynucleoside adduction varied based on CE structure and deoxynucleoside type, forming both stable and deglycosylated adducts.
- MS(2) and MS(3) experiments elucidated the regiochemistry of steroid moiety adduction.
Conclusions:
- CE can form stable adducts with DNA, potentially leading to DNA strand breaks or loss of purines.
- The specific CE and deoxynucleoside structures influence the type and stability of adducts formed.
- Understanding these adducts is crucial for assessing the genotoxic risk of estrogens.