Receptor independent effects on DNA replication by steroids.
There is now convincing evidence associating estrogens with an increased risk of some cancers. However, the absence of a complete correlation between estrogen receptor binding and the biological activity of these estrogens has suggested the possibility of other mechanisms of action. The effect on DNA replication of several hormones that are putatively involved in breast cancer was tested at a physiological concentration. The studies were conducted in a HeLa cell-free system by using a plasmid containing a specific mammalian origin of replication (DHFR ori beta) as template DNA. A series of related steroids produced an entire range of activity from enhancement to inhibition of in vitro DNA replication. These studies indicate a new possible target, which may help to better understand the effect of these hormones in breast cancer. Furthermore, the results show that this in vitro DNA replication system provides an evaluative assay for the effects of compounds on hormone-responsive cancers independent of some hormone receptors.
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
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Diaz-Perez
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Zannis-Hadjopoulos
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Price
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Wainer
D002474:Cell-Free System; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects*; D015252:Deoxyribonucleases, Type II Site-Specific; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D004964:Estriol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D004970:Estrone / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D009711:Nucleotides / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000032:analysis*; D013739:Testosterone / Q000494:pharmacology
D004967:Estrogens; D009711:Nucleotides; D011960:Receptors, Estrogen; D004970:Estrone; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D004247:DNA; C020102:endodeoxyribonuclease DpnI; D015252:Deoxyribonucleases, Type II Site-Specific; D004964:Estriol