Add time:08/07/2019 Source:sciencedirect.com
The concentrations of tamoxifen and two of its metabolites, N-desmethyltamoxifen and 4′-hydroxytamoxifen (metabolite B), have been measured in rat plasma and DMBA-induced tumours using gas chromatography-mass spectrometry. At a dose of 100 μg/day all three compounds produced tumour regression and, in the case of tamoxifen, the number and extent of regressions and the inhibition of new tumours were dependent upon dosage. No correlation was observed, however, between tumour regression and the concentrations of tamoxifen or N-desmethyltamoxifen in the plasma of individual animals. When tamoxifen, N-desmethyltamoxifen and metabolite B were measured in oestrogen-receptor-positive tumours a correlation was found between reduction in tumour and the tamoxifen concentration in cytosol fractions. The concentrations of all three compounds in both nuclear and cytosol fractions were higher than could be accounted for by binding to the oestrogen receptor. The mechanistic significance of these high values is, at present, unclear.
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