Relative carcinogenic activity of various synthetic and natural estrogens in the Syrian hamster kidney.
Relative carcinogenic activity of various synthetic and natural estrogens in the Syrian hamster kidney.
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DOI：
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发表时间：
1983-11
期刊：
影响因子：
11.2
通讯作者：
J. Li;S. Li;J. Klicka;J. Parsons;L. Lam
中科院分区：
文献类型：
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作者：
J. Li;S. Li;J. Klicka;J. Parsons;L. Lam
已经研究了合成和天然雌激素在去势雄性仓鼠中治疗9.0个月后诱导肾癌的能力。肿瘤病灶检测冷冻连续切片染色雌激素酶活性。己烯雌酚（DES）和17 β-雌二醇诱导肾肿瘤的能力相同（100%）[约20.5 +/- 3（S.E.）肿瘤病灶]。己烷雌酚诱导的肾癌病灶的发生率和数量与DES或17 β-雌二醇相同。然而，α-二烯雌酚和DES 3，4-氧化物显示仓鼠肾肿瘤的发生率为86 - 88%（约10.8 +/- 3）。当马烯雌酚和d-马烯雌酚（治疗性结合雌激素的成分）被检测时，只有马烯雌酚具有76%的肾肿瘤病灶发生率（5.5 +/- 0.9）。这些芪类和甾体类雌激素竞争肾肿瘤雌激素受体的能力通常与其在仓鼠中引起肾肿瘤发生的能力相关，但有一个明显的例外。尽管炔雌醇与DES或17 β-雌二醇竞争雌激素受体，具有相似的诱导肾孕酮受体的能力，并导致与DES或17 β-雌二醇相似的高血清催乳素水平，但其在仓鼠肾脏（0.6 +/- 0.5个病灶）中仅具有弱致癌活性（21%）。这些数据代表了在给定的肿瘤诱导系统中不同雌激素的相对致癌活性的第一次详细分析，并且基于本文中提供的己烷雌酚和α-二烯雌酚的致癌性数据，它们表明DES的烯双键和对醌代谢物的环氧化可能不显著参与其致癌活性。此外，乙炔雌二醇在该系统中的不良致癌活性，尽管具有强雌激素活性，表明雌激素活性本身可能不足以影响仓鼠的肾肿瘤发生。
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.