Dietary quercetin exacerbates the development of estrogen-induced breast tumors in female ACI rats.

Dietary quercetin exacerbates the development of estrogen-induced breast tumors in female ACI rats.
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膳食槲皮素会加剧雌性 ACI 大鼠雌激素诱导的乳腺肿瘤的发展。

DOI:
10.1016/j.taap.2010.06.011
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发表时间:
2010
影响因子:
3.8
通讯作者:
Bhat,HariK
Bhat,HariK
中科院分区:
医学3区
文献类型:
--
作者:
Singh,Bhupendra;Mense,SarahM;Bhat,NimeeK;Putty,Sandeep;Guthiel,WilliamA;Remotti,Fabrizio;Bhat,HariK

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植物雌激素是一类在结构上模拟内源雌激素17-雌二醇(β-estadiol,E_2)的植物化合物。尽管进行了密集的调查,但暴露于植物雌激素对乳房的净影响仍不清楚。本研究的目的是在体内检测槲皮素对雌激素诱导的乳腺癌的影响。雌性ACI大鼠按2.5g/kg饲料灌胃,连续8个月。每周监测动物是否有可触及的肿瘤,在实验结束时,对大鼠实施安乐死,切除乳腺肿瘤和不同组织,以便检查它们的组织病理学变化、雌激素代谢活性和氧化应激。在雌性ACI大鼠中,单用Qercetin不能诱发乳腺肿瘤。然而,在植入E2颗粒的大鼠中,共同暴露于栎素并不能保护大鼠免受E2诱导的乳腺肿瘤的发展,100%的动物在治疗后8个月内发生乳腺肿瘤。实验结束时,槲皮素组和槲皮素+雌二醇组大鼠血清中的槲皮素水平未见明显变化。与雌二醇组相比,槲皮素+雌二醇组大鼠的肿瘤潜伏期显著缩短。儿茶酚-O-甲基转移酶(COMT)活性在暴露于栎素的乳腺组织中显著下调。8-异前列腺素F2α(8-iso-PGF_2α)水平作为氧化应激指标的分析表明,槲皮素不能减轻E_2诱导的氧化应激。这些结果表明,栎素(2.5g/kg食物)对乳腺癌没有保护作用,也没有抑制E2诱导的氧化应激,而且可能会加剧E2处理的ACI大鼠的乳腺癌形成。用槲皮素抑制COMT活性可能会使乳腺细胞长期暴露于E2和儿茶酚雌激素。这将允许更长的时间接触致癌的E2代谢物,以及由于代谢氧化还原循环到雌激素代谢物而长期暴露于氧化应激,因此Qercetin可能会加剧雌性ACI大鼠由E2诱导的乳腺肿瘤。
Phytoestrogens are plant compounds that structurally mimic the endogenous estrogen 17β-estradiol (E2). Despite intense investigation, the net effect of phytoestrogen exposure on the breast remains unclear. The objective of the current study was to examine the effects of quercetin on E2-induced breast cancer in vivo. Female ACI rats were given quercetin (2.5g/kg food) for 8months. Animals were monitored weekly for palpable tumors, and at the end of the experiment, rats were euthanized, breast tumor and different tissues excised so that they could be examined for histopathologic changes, estrogen metabolic activity and oxidant stress. Quercetin alone did not induce mammary tumors in female ACI rats. However, in rats implanted with E2pellets, co-exposure to quercetin did not protect rats from E2-induced breast tumor development with 100% of the animals developing breast tumors within 8months of treatment. No changes in serum quercetin levels were observed in quercetin and quercetin+E2-treated groups at the end of the experiment. Tumor latency was significantly decreased among rats from the quercetin+E2group relative to those in the E2group. Catechol-O-methyltransferase (COMT) activity was significantly downregulated in quercetin-exposed mammary tissue. Analysis of 8-isoprostane F2α(8-iso-PGF2α) levels as a marker of oxidant stress showed that quercetin did not decrease E2-induced oxidant stress. These results indicate that quercetin (2.5g/kg food) does not confer protection against breast cancer, does not inhibit E2-induced oxidant stress and may exacerbate breast carcinogenesis in E2-treated ACI rats. Inhibition of COMT activity by quercetin may expose breast cells chronically to E2and catechol estrogens. This would permit longer exposure times to the carcinogenic metabolites of E2and chronic exposure to oxidant stress as a result of metabolic redox cycling to estrogen metabolites, and thus quercetin may exacerbate E2-induced breast tumors in female ACI rats.
用金胶体颗粒标记细胞表面:使用抗生物素蛋白和葡萄球菌蛋白 A 包被的金与生物素和带有 fc 的配体结合使用
DOI: 10.1111/j.1365-2818.1981.tb01296.x
发表时间: 1981
影响因子: 2
作者:
N. Tolson;B. Boothroyd;C. Hopkins
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DOI: --
发表时间: 1977
期刊:
影响因子: --
作者:
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DOI: 10.1073/pnas.78.1.368
发表时间: 1981
影响因子: 11.1
作者:
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DOI: --
发表时间: 1974
期刊: Immunochemistry
影响因子: --
作者:
E. Romano;C. Stolinski;N. Hughes
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DOI: 10.1083/jcb.75.2.528
发表时间: 1977-11
期刊: The Journal of cell biology
影响因子: --
作者:
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通讯作者: Gregory H