Strain differences in response to diethylstilbestrol and the induction of mammary gland and bladder cancer in the rat.

Abstract

The response of 3 inbred lines of rats to unphysiological stimulation from diethylstilbestrol are reported. Pellets of compressed crystalline diethylstilbestrol weighing 15-25 mg were implanted in the scapular region of 30 rats of both sexes of each of 3 distinct inbred lines and were replaced individually as soon as the previous pellet was completely absorbed. The rats of the 3 lines varied in survival and in the absorption rate of the diethylstilbestrol. Rats of Fischer line 344 succumbed first after the most rapid absorption of the hormone. Females of this line lived an average of only 67 days and absorbed an average of 19 mg/rat. The males survived an average of 136 days and absorbed 29 mg/rat. The Copenhagen line 2331 males survived for 289 days and the females for 200 days having absorbed an average of 38 and 30 mg of hormone respectively. The rats of A X C line 9935 were intermediate; the males survived for 167 days and the females for 186 days in which time the average absorption of diethylstilbestrol was 24 and 25 mg/rat. The most conspicuous pathological lesions included pituitary adenomas fatty livers and bladder calculi and papillomas. Pronounced strain differences were observed in the expression of these lesions. Pellets of 75% cholesterol containing 4-15 mg of diethylstilbestrol were implanted in the scapular region of a 2nd and similar series of rats and no reimplantations were necessary to keep the rats in a constant state of hyperestrinism for the remainder of their lives. The average survival period for the Fischer line 344 rats was increased to 200 days for the females and 367 days for the males with the more slowly absorbed diethylstilbestrol. The A X C males lived an average of 388 days and the females 422 days whereas the Copenhagen males and females survived 528 days and 499 days respectively. Mammary cancer was observed in 17 or 80% of the A X C males in 22 of 85% of the A X C females. Only 1 or 17% of the Fischer line 344 females and 5 or 22% of the Fischer line 344 males had mammary cancer. No mammary cancers were observed in treated male or female Copenhagen line 2331 rats but 16 or 62% of the males and 6 or 29% of the females had either bladder papillomas or squamous cell cancer associated with urinary calculi.