Relative Carcinogenic Activity of Various Synthetic and Natural Estrogens in the Syrian Hamster Kidney1

نویسندگان

  • Jonathan J. Li
  • Sara Antonia Li
  • John K. Klicka
  • Jonathan A. Parsons
  • Luke K. T. Lam
چکیده

Both synthetic and natural estrogens have been studied for their ability to induce renal carcinomas in castrated male ham sters after 9.0 months of treatment. Tumor foci were detected in frozen serial sections stained histochemically for esterase activity. Both diethylstilbestrol (DES) and 17.^-estradiol had equal ability (100%) to induce renal tumors [~20.5 ±3 (S.E.) tumor foci] in these animals. Hexestrol induced the same incidence and number of renal carcinoma foci as DES or 17/3-estradiol. How ever, a-dienestrol and DES 3,4-oxide showed an 86 to 88% incidence of renal tumors in hamsters (~10.8 ±3). When equilin and d-equilenin, components of therapeutic conjugated estro gens, 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 gener ally 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 17/3-estradiol for estrogen receptor, had similar ability to induce renal progester one receptor, and led to similar high serum prolactin levels as either DES or 17/3-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 a-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.

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Estrogens in the Syrian Hamster Kidney Relative Carcinogenic Activity of Various Synthetic and Natural

Both synthetic and natural estrogens have been studied for their ability to induce renal carcinomas in castrated male ham sters after 9.0 months of treatment. Tumor foci were detected in frozen serial sections stained histochemically for esterase activity. Both diethylstilbestrol (DES) and 17.^-estradiol had equal ability (100%) to induce renal tumors [~20.5 ±3 (S.E.) tumor foci] in these anim...

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Relative carcinogenic activity of various synthetic and natural estrogens in the Syrian hamster kidney.

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 foc...

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Estrogen 2- and 4-hydroxylase activity, catechol estrogen formation, and implications for estrogen carcinogenesis in the hamster kidney.

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تاریخ انتشار 2006