Antimitotic steroidal estrogens

OR several years the laboratory of one of US F (R1.N.H.) has been concerned with the finding of a superior estrogen for therapy of prostatic cancer. We have desired a molecule that had three attributes: (1) it should belong to the naturally occurring steroid group; (2) it should have definite but weak biological potency in terms of the Allen-Doisy assay; and (3) it should hate strong antimitotic, or as it is commonly termed in Europe, particularly in Germany, “cystostatic,” action. First permit us to say that we have paid no attention to pituitary relationships. We realize that all the premises upon which we have based our objectives may be invalid so lar as the final end point of treatment of cancer of the prostate is concerned. We have had two testing programs available to us; one 01 these utilizes the standard tissueculture method; the second one is a newly developed fish-egg test similar to the European sea urchin-egg test. We should like to present the data with the fibroblast technique first, This screening program, under one OP us (A.4.K.), utilized the heart fibroblast from the chick embryo. At the start of our experiments we used as an end point the growth of the explant from the tissue culture. We finally decided this was a poor end point; but after we had assayed some two dozen steroidal estrogens we observed that two were very much more active than the rest. Thcse were, surprisingly enough to us, the compounds 16-ketoestrone and 16-ketoestradiol. It was felt by one of us (A.A.K.) that the indexes for measuring antimitotic effects should be changed, especially after it had been found that the effect was one of typical metaphase arrest, or the typical colchicine effect, in mitosis. (This was alluded to by von Mollendorff 3