Diethyl Stilbestrol Excretion in Tumor-Bearing Rabbits *

Stroud' has shown in rabbits that diethyl stilbestrol is excreted in the urine in concentrations far exceeding those of the naturally occurring estrogens, and that the major part of the administered drug is recovered in the unconjugated state. Von Hamm7 found in human beings that 10 to 30 per cent of injected diethyl stilbestrol was eliminated in 10 days. Excretion curves showed that the maximum output was reached in from 48 to 72 hours. Mazer5 et al. gave single doses of diethyl stilbestrol to castrate women hypodermically and found a maximum excretion in from 24 to 48 hours. The results of these investigators were based upon bio-assay methods. Dingemanse,2 however, has proposed a colorimetric method using SbCI5. Using this technic, Dingemanse and Tyslowitz3 have reported that in dogs it is possible to recover 50 per cent of the administered estrogen with from 8 to 25 per cent present in the urine. It seemed to us that diethyl stilbestrol might prove a useful tool in advancing our knowledge of estrogen metabolism in relation to carcinogenesis, since it is excreted in sufficent quantity to make metabolism studies feasible. Moreover, if natural enzyme systems dealing with estrogen metabolism are at fault in carcinogenesis, diethyl stilbestrol might be a convenient precursor substrate to disdose such perverted utilization of natural sterols. The present investigation is concerned primarily with the excretion of diethyl stilbestrol in the urine of normal rabbits and of rabbits which have malignant tissues growing in the anterior chamber of the eye. Subsequent studies will deal with body tumors, both implanted and spontaneous. Methods Young adult rabbits weighing from 1.8 to 2.5 kg. were maintained in metabolism cages on a diet of dry commercial rabbit chow and water. The cancer-bearing animals were litter mates and had been prepared by injection