The biological activities of diethylstibestrol (DES) of 17 beta-oestradiol (17 beta E) were initially tested, based on the uterus enlargement induced by different doses given with food to immature female mice. In a second series of experiments, the drugs were given in higher doses per os to rats (relay animals) and after 24 h, the livers of the relay rats were removed. Parts of the livers were freeze-dried and were added (10% w/w) to the food of immature female mice, while the remainder underwent chemical analysis to determine the DES and 17 beta E content. When given directly to mice with their food, DES showed about six times more biological activity than 17 beta E. When given through the livers of relay rats, the biological activity of the livers from DES-and 17 beta E-treated relay rats was of the same magnitude. The content of 17 beta E in the livers of relay rats was 10-20 times higher than the DES. Such concentrations corresponded directly to the biological activity of livers. These data show that the bioavailability and the relative potency of xenobiotic drugs and natural hormones may be profoundly altered after passing through metabolic pathways, and may give useful indications for the evaluation of biological activity of residues and contaminants and their metabolites in the food.
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