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Carcinogenic antioxidants. Diethylstilboestrol, hexoestrol and 17 alpha-ethynyloestradiol
1Pharmacology Group, King's College, University of London, UK.
Abstract:
The synthetic oestrogens diethylstilboestrol, hexoestrol and 17 alpha-ethynyloestradiol are known to be carcinogenic, yet they all exert antioxidant properties in vitro in that they are good inhibitors of iron ion-dependent lipid peroxidation. In rat liver microsomes incubated with Fe(III)-ascorbate or Fe(III)-ADP/NADPH and also in ox-brain phospholipid liposomes incubated with Fe(III)-ascorbate; the overall order of effectiveness of the compounds tested as inhibitors of lipid peroxidation was diethylstilboestrol > hexoestrol > 17 alpha-ethynyloestradiol > 4-hydroxytamoxifen > 17 beta-oestradiol > tamoxifen. Compounds acting as antioxidants towards lipids may also exert pro-oxidant effects towards other molecules such as DNA and thus must never be assumed to be safe for human use.
Insights
Synthetic estrogens like diethylstilbestrol show antioxidant effects by inhibiting lipid peroxidation in vitro. However, these compounds may also have pro-oxidant effects on DNA, highlighting potential risks despite their antioxidant properties.
Area of Science:
- Endocrinology
- Biochemistry
- Toxicology
Background:
- Synthetic estrogens, including diethylstilbestrol (DES), hexoestrol, and 17 alpha-ethynyloestradiol, are recognized carcinogens.
- Despite their carcinogenic nature, these compounds exhibit antioxidant properties in vitro.
Purpose of the Study:
- To investigate the antioxidant capacity of synthetic estrogens by examining their ability to inhibit iron ion-dependent lipid peroxidation.
- To compare the effectiveness of various synthetic estrogens and related compounds as inhibitors of lipid peroxidation.
Main Methods:
- In vitro assays using rat liver microsomes and ox-brain phospholipid liposomes.
- Incubation with iron(III) (Fe(III)) in the presence of ascorbate or ADP/NADPH to induce lipid peroxidation.
- Quantification of inhibition of lipid peroxidation by different synthetic estrogen compounds.
Main Results:
- All tested synthetic estrogens demonstrated inhibitory effects on iron ion-dependent lipid peroxidation.
- The order of effectiveness as lipid peroxidation inhibitors was diethylstilbestrol > hexoestrol > 17 alpha-ethynyloestradiol > 4-hydroxytamoxifen > 17 beta-oestradiol > tamoxifen.
- Compounds effective against lipid peroxidation may pose pro-oxidant risks to other biomolecules like DNA.
Conclusions:
- Synthetic estrogens possess in vitro antioxidant activity against lipid peroxidation.
- The dual antioxidant/pro-oxidant potential necessitates caution regarding their safety for human use.
- Further research is required to fully elucidate the complex biological effects of these compounds.