Tamoxifen and related compounds protect against lipid peroxidation in isolated nuclei: relevance to the potential anticarcinogenic benefits of breast cancer prevention and therapy with tamoxifen?
Tamoxifen, 4-hydroxytamoxifen, nafoxidine, 17 beta-oestradiol and ICI 164,384 were all found to protect rat liver nuclei against Fe(III)-ascorbate dependent lipid peroxidation. The order of effectiveness of these compounds was 4-hydroxytamoxifen > 17 beta-oestradiol > nafoxidine > tamoxifen > ICI 164,384. This protection by tamoxifen against the formation of the genotoxic reactive-intermediates and products of lipid peroxidation in the nuclear membrane could be important in the prevention of nuclear DNA damage and thus carcinogenesis. This possible anticarcinogenic benefit of tamoxifen treatment could be important in long-term therapy with tamoxifen (and future derivatives) and in its proposed use in the prevention of breast cancer.
Pharmacology Group, King's College, University of London, UK.
H
H
Wiseman
B
B
Halliwell
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000517:prevention & control*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009256:Nafoxidine / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use*
D016588:Anticarcinogenic Agents; D004965:Estrogen Antagonists; D053284:Polyunsaturated Alkamides; D013629:Tamoxifen; C016601:afimoxifene; D009256:Nafoxidine; D004958:Estradiol; C051781:ICI 164384