STUDIES ON THE CONVERSION OF OESTRADIOL LINKED TO A CYTOSTATIC AGENT (ESTRACYT®) IN VARIOUS RAT TISSUES

Abstract

ABSTRACT Estracyt®, a compound of nitrogen-mustard linked to oestradiol phosphate, is used in the treatment of human prostatic cancer. The metabolism of this compound has been studied in different tissues of the rat both in vivo and in vitro. The phosphate group in position 17 of the oestradiol moiety is rapidly split off from the compound. An oestrone-cytostatic compound was extractable from the liver half an hour after the injection of Estracyt®. In addition the in vitro results showed that only the liver was able to convert the oestradiol-cytostatic compound to an oestrone-cytostatic one. When animals were killed 24 h after a 3-day period of Estracyt® treatment, the dominating metabolite in the ventral prostate was an oestrone-cytostatic compound, but traces of free oestrone could also be demonstrated. No such compound, however, was found in liver, diaphragm or blood at this time. It is concluded that in vivo an oestrone-cytostatic compound seems to be preferentially retained in the ventral prostate after Estracyt® injection whilst the metabolic conversion of the oestradiol-cytostatic compound into an oestrone-cytostatic one possibly occurs in the liver.