The effect of different L-histidine concentrations on human mammary tumour cell (CG5) proliferation was studied to test the hypothesis of a role of histidine in modulating sex steroid-regulated cell proliferation. Cell growth was only possible in the 10(-5) M and 10(-2) M range, while its inhibition by medroxyprogesterone acetate was confined to the 10(-4) M and 10(-3) M range. 10(-3) M L-histidine enhanced the effect of medroxyprogesterone acetate in reducing the number of cells in the S phase. The results show also that 10(-3) M L-histidine favours progestin diffusion into cells and increases progestin receptors density. The present data are in line with previous observations of the effect of histidine on the growth of experimental animal tumours, add evidence that histidine concentration influences the control of cell proliferation by sex steroids, and suggest a possible use of histidine in association with progestational drugs in the treatment of human neoplasia.
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