PROMOTIVE EFFECTS OF DIETHYLSTILBESTROL, ITS METABOLITE (Z,Z-DIENESTROL) AND A STEREOISOMER OF THE METABOLITE (E,E-DIENESTROL) IN TUMORIGENESIS OF RAT MAMMARY-GLANDS PREGNANCY-DEPENDENTLY INITIATED WITH RADIATION
PROMOTIVE EFFECTS OF DIETHYLSTILBESTROL, ITS METABOLITE (Z,Z-DIENESTROL) AND A STEREOISOMER OF THE METABOLITE (E,E-DIENESTROL) IN TUMORIGENESIS OF RAT MAMMARY-GLANDS PREGNANCY-DEPENDENTLY INITIATED WITH RADIATION
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DOI：
10.1093/carcin/14.10.2157
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发表时间：
1993-10-01
期刊：
影响因子：
4.7
通讯作者：
WAKABAYASHI, K
中科院分区：
文献类型：
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作者：
INANO, H;SUZUKI, K;WAKABAYASHI, K
Wistar-MS大鼠在妊娠第20天接受260 cGy γ射线全身照射，然后用己烯雌酚（DES）、E，E-双烯雌酚（E，E-DES）或Z，Z-双烯雌酚（Z，Z-DES）治疗1年。DES给药导致乳腺肿瘤的发生率最高，同时体重增加减少。当以颗粒形式植入E，E-III或Z，Z-III时，肿瘤的发生率显著低于用DES治疗的大鼠中观察到的。为了阐明DES给药后乳腺肿瘤发生的易感性增加，我们测量了植入含有合成雌激素衍生物的颗粒的大鼠血清中的激素水平。血清催乳素浓度显着增加DES管理。当植入E，E-ESTA或Z，Z-ESTA颗粒的催乳素水平显着降低到4.5%和0.7%，在DES治疗的大鼠中观察到的，分别。此外，Z，Z-E17-β颗粒剂组大鼠血清雌二醇和孕酮浓度高于DES或E，E17-β颗粒剂组。大量DES诱导的乳腺肿瘤雌激素和孕激素受体均呈阳性，但没有获得两种受体阴性的肿瘤。结果表明，DES直接作用于辐射引发的乳腺细胞通过与雌激素受体结合和/或刺激垂体分泌催乳素。
Wistar-MS rats received whole body irradiation with 260 cGy gamma-rays at day 20 of pregnancy and then were treated with diethylstilbestrol (DES), E,E-dienestrol (E,E-DIES) or Z,Z-dienestrol (Z,Z-DIES) for 1 year. DES administration caused the highest incidence of mammary tumors with a concomitant reduction of gain in body weight. When E,E-DIES or Z,Z-DIES in pellet form was implanted, the incidence of tumors was significantly lower than that observed in rats treated with DES. To clarify the increased susceptibility to mammary tumorigenesis after DES administration we measured hormone levels in the serum of rats implanted with pellets containing derivatives of the synthetic estrogens. The serum prolactin concentration was significantly increased by DES administration. When E,E-DIES or Z,Z-DIES pellets were implanted the prolactin level was markedly reduced to 4.5% and 0.7% of that observed in DES-treated rats, respectively. In addition, the serum concentrations of estradiol-17beta and progesterone in rats with Z,Z-DIES pellets were higher than those of rats with DES or E,E-DIES pellets. A large number of DES-induced mammary tumors were positive for both estrogen and progesterone receptors, but no tumors negative for both receptors were obtained. The findings suggest that DES acts directly on radiation-initiated mammary cells via binding with estrogen receptors and/or stimulates the secretion of prolactin from the pituitary glands.