Mammary tumorigenesis in C3H/HEN-MTV + mice treated with diethylstilboestrol for varying periods

C3H/HeN-MTV + female mice were fed diets containing 320 or 640 ppb diethylstilboestrol (DES). DES feeding was started at 3 wk of age and was either continued throughout life or discontinued after 4, 8 or 26 wk of administration. A control group consisted of mice fed the same diet without DES, for the duration of the experiment. Mice were killed when palpable body masses (presumed to be mammary adenocarcinomas) reached a diameter of 1 cm. Adenocarcinomas developed in 79% of control mice and 96% of the mice exposed to DES for 26 wk, irrespective of the dose. The frequency and rate of removal of tumour-bearing mice were not increased further with lifetime exposure at a given dose. The time at which the first tumour occurred was largely dependent on the duration of exposure, not dose. The rate of occurrence of subsequent tumours was dependent on dose and duration of exposure; the rate of removal of mice with mammary adenocarcinomas was significantly greater at 640 ppb than at 320 ppb DES. Tumour frequency was 83% in mice exposed to 320 ppb DES for 8 wk and in those exposed for 4 wk; however, tumours developed at a faster rate in mice exposed for 8 wk. Tumour frequency was 94–96% in mice exposed to 640 ppb DES for 4 wk and 8 wk, and tumours developed more rapidly in mice exposed for 8 wk than in those exposed for 4 wk. When data were plotted as log-dose v. log-t 50 (time to a probability that half the mice would be removed with mammary tumours) linear extrapolation to the control log-t 50 gave an estimate of the no-effect level of exposure to DES. This estimate was remarkably consistent for all data sets (40–93 ppb) and was independent of the duration of exposure.