Early increases in ribonucleic acid polymerase activities of dimethylbenzanthracene-induced mammary tumour nuclei in response to oestradiol-17beta and tamoxifen.
Studies on the mode of action of tamoxifen have shown that this compound ultimately causes regression of mammary tumours induced in female rats by 7,12-dimethylbenz(a)-anthracene, but induces preliminary effects similar to those produced by oestradiol-17beta. Following a single intravenous injection of either substance, a sequence of events was observed which included depletion of cytoplasmic receptor, a concomitant increase in nuclear receptor and a subsequent replenishment of cytoplasmic receptor. Tamoxifen and oestradiol-17beta induced a transient increase in RNA polymerase B activity, followed by increases in RNA polymerase A and, again, RNA polymerase B activity. Tamoxifen, unlike oestradiol-17beta, could not maintain replenishment of cytoplasmic receptor, the increase in RNA polymerase A activity or the secondary rise in RNA polymerase B activity. The basic anti-oestrogenic properties of tamoxifen may be implicit in its inability to maintain oestrogen stimulation, and may be linked to its retention time within the nuclei.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000201:enzymology*; D051381:Rats; D011960:Receptors, Estrogen / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology*; D013997:Time Factors
D011960:Receptors, Estrogen; D013267:Stilbenes; D013629:Tamoxifen; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene; D012321:DNA-Directed RNA Polymerases