Both synthetic and natural
estrogens have been studied for their ability to induce
renal carcinomas in castrated male hamsters after 9.0 months of treatment.
Tumor foci were detected in frozen serial sections stained histochemically for estrase activity. Both
diethylstilbestrol (DES) and
17 beta-estradiol had equal ability (100%) to induce renal
tumors [approximately 20.5 +/- 3 (S.E.)
tumor foci] in these animals.
Hexestrol induced the same incidence and number of
renal carcinoma foci as DES or
17 beta-estradiol. However, alpha -
dienestrol and DES 3,4-oxide showed an 86 to 88% incidence of renal
tumors in hamsters (approximately 10.8 +/- 3). When
equilin and d-
equilenin, components of therapeutic
conjugated estrogens, were tested, only
equilin had a 76% incidence of renal
tumor foci (5.5 +/- 0.9). The ability of these
stilbene and steroidal
estrogens to compete for renal
tumor estrogen receptor generally correlated well with their ability to cause renal
tumorigenesis in the hamster with one notable exception. Although
ethinyl estradiol competed as well as did DES or
17 beta-estradiol for
estrogen receptor, had similar ability to induce renal
progesterone receptor, and led to similar high serum
prolactin levels as either DES or
17 beta-estradiol, it had only weak carcinogenic activity (21%) in the hamster kidney (0.6 +/- 0.5 foci). These data represent the first detailed analysis of the relative carcinogenic activity of different
estrogens within a given
tumor-inducing system, and based on the carcinogenicity data of
hexestrol and alpha-
dienestrol presented herein, they suggest that epoxidation of the olefinic double bond and the p-
quinone metabolite of DES probably are not involved significantly in its carcinogenic activity. Moreover, the poor carcinogenic activity of
ethinyl estradiol in this system, despite strong estrogenicity, suggests that estronic activity alone may not be sufficient to effect renal
tumorigenesis in the hamster.