Studies on a Nitrogen Mustard of Estradiol in Dogs and Rats 1

Abstract

Summary

Estracyt, a conjugate of 17 β-estradiol (E₂) and a cytotoxic agent (carba-mate), labeled with ³H in its E₂ moiety was administered to dogs and rats and the fate of the compound was compared to that of coadministered [¹⁴C]E₂. Excretion of radio-activity was determined in bile and urine and the excretory patterns were established by CCD. This approach allows a determination of the hydrolysis of the estracyt molecule by comparing the behavior of the two labels. In the dog, the radioactivities appeared in the bile and urine at the same rate, indicating ready hydrolysis of the estracyt. In the rat, however, the ³H was excreted at a much slower rate with very small amounts appearing in the urine within 24 hr and relatively large amounts appearing in the bile; however, most of the estracyt was retained in the body of the rat. When hydrolysis takes place in the dog and rat, the released E₂ behaves similarly to that of administered E₂.