Prepubertal exposure to zearalenone or genistein reduces mammary tumorigenesis.
Prepubertal exposure to zearalenone or genistein reduces mammary tumorigenesis.
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DOI：
10.1038/sj.bjc.6690584
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发表时间：
1999-08
影响因子：
8.8
通讯作者：
Clarke, R
中科院分区：
文献类型：
--
作者：
Hilakivi-Clarke, L;Onojafe, I;Raygada, M;Cho, E;Skaar, T;Russo, I;Clarke, R
在大鼠中，青春期前暴露于药理学剂量（500 mg kg - 1）的植物雌激素染料木素可以减少致癌物质诱导的乳腺肿瘤的发生率和多样性。然而，这种暴露也会破坏下丘脑-垂体-性腺轴的功能，使其不适合预防乳腺癌。我们研究了青春期前暴露于染料木素的总剂量与东方国家的典型水平大致相当，大约1 mg kg - 1体重，是否会影响乳腺肿瘤的发生。我们还研究了青春期前接触玉米赤霉烯酮是否会影响乳腺癌风险，玉米赤霉烯酮是美国植物雌激素的主要来源。在出生后第7天至第20天，给青春期前大鼠注射染料木黄酮或玉米赤霉烯酮各20 μg （~ 1 mg kg - 1体重）。玉米赤霉烯酮暴露可显著降低7,12-二甲基苯(a)蒽（DMBA）诱导的乳腺肿瘤的发生率和多样性。与药物处理的动物相比，染料木素暴露显著降低了肿瘤的多样性，但没有降低肿瘤的发病率。此外，染料木素组中60%的肿瘤不是恶性的，而在载体和玉米赤霉烯酮组中进行组织病理学分析的所有肿瘤都是腺癌。植物雌激素暴露大鼠经dba处理的乳腺中，分化的肺泡芽数量较多，末梢导管数量较少。DMBA处理后，各组乳腺中雌激素受体（ER）结合位点的浓度均较低，但玉米赤霉烯酮暴露大鼠乳腺中ER阳性（即ER水平≥5 fmol mg - 1蛋白）的比例明显高于对照。我们的数据表明，青春期前暴露于低剂量的玉米赤霉烯酮或染料木素可能通过增加乳腺上皮树的分化来保护乳腺免受致癌物诱导的恶性转化。©1999癌症研究运动
Prepubertal exposure to a pharmacological dose (500 mg kg−1) of the phyto-oestrogen genistein can reduce the incidence and multiplicity of carcinogen-induced mammary tumours in rats. However, such an exposure also disrupts the function of the hypothalamic–pituitary–gonadal axis, making it unsuitable for breast cancer prevention. We studied whether prepubertal exposure to genistein at a total body dose broadly comparable to the level typical of Oriental countries, approximately 1 mg kg−1 body weight, affects mammary tumorigenesis. We also studied whether prepubertal exposure to zearalenone, a major source for phyto-oestrogens in the USA, influences breast cancer risk. Prepubertal rats were treated between postnatal days 7 and 20, with 20 μg (~ 1 mg kg−1 body weight) of either genistein or zearalenone. Zearalenone exposure significantly reduced both the incidence and multiplicity of mammary tumours induced by 7,12-dimethylbenz(a)anthracene (DMBA). Genistein exposure significantly reduced tumour multiplicity, but not tumour incidence, when compared with vehicle-treated animals. Furthermore, 60% of the tumours in the genistein group were not malignant, while all the tumours analysed for histopathology in the vehicle and zearalenone groups were adenocarcinomas. A higher number of differentiated alveolar buds, and lower number of terminal ducts, were present in the DMBA-treated mammary glands of the phyto-oestrogen exposed rats. The concentration of oestrogen receptor (ER) binding sites after the DMBA treatment was low in the mammary glands of all groups but a significantly higher proportion of the glands in the zearalenone exposed rats were ER-positive (i.e. ER levels ≥ 5 fmol mg−1 protein) than the glands of the vehicle controls. Our data suggest that a prepubertal exposure to a low dose of either zearalenone or genistein may protect the mammary gland from carcinogen-induced malignant transformation, possibly by increasing differentiation of the mammary epithelial tree. © 1999 Cancer Research Campaign
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影响因子：
4.3
作者：
Fukutake, M;Takahashi, M;Wakabayashi, K
通讯作者：
Wakabayashi, K
影响因子：
4.2
作者：
HAWRYLEWICZ, EJ;HUANG, HH;BLAIR, WH
通讯作者：
BLAIR, WH
影响因子：
168.9
作者：
EKBOM, A;TRICHOPOULOS, D;LAN, SJ
通讯作者：
LAN, SJ
影响因子：
4.8
作者：
HASLAM, SZ
通讯作者：
HASLAM, SZ
影响因子：
168.9
作者：
LEE, HP;GOURLEY, L;DAY, NE
通讯作者：
DAY, NE