EARLY INCREASES IN RIBONUCLEIC ACID POLYMERASE ACTIVITIES OF DIMETHYLBENZANTHRACENE-INDUCED MAMMARY TUMOUR NUCLEI IN RESPONSE TO OESTRADIOL-17β AND TAMOXIFEN

in Journal of Endocrinology
Authors:
R. I. NICHOLSON
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P. DAVIES
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K. GRIFFITHS
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SUMMARY

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-17β. 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-17β 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-17β, 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 oestrogenic stimulation, and may be linked to its retention time within the nuclei.

 

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