Chemopreventive effects of soy protein and purified soy isoflavones on DMBA-induced mammary tumors in female Sprague-Dawley rats

Chemopreventive effects of soy protein and purified soy isoflavones on DMBA-induced mammary tumors in female Sprague-Dawley rats
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DOI:
10.1207/s15327914nc41-1
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发表时间:
2001-01-01
影响因子:
2.9
通讯作者:
Pezzuto, JM
Pezzuto, JM
中科院分区:
医学4区
文献类型:
--
作者:
Constantinou, AI;Lantvit, D;Pezzuto, JM

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大豆及其成分对成年雌性大鼠乳腺癌发生的影响存在相互矛盾的报道,主要是因为化学预防研究中使用的啮齿动物模型不同。本研究是进行比较的肿瘤预防作用的大豆分离蛋白(SPI)和它的两个主要的“标准”模型,已被用于识别许多化学预防剂。向六组雌性Sprague-Dawley大鼠提供如下补充的改性玉米淀粉AIN-76 A饮食:无额外试剂(对照)、纯化的染料木黄酮(200 mg/kg饮食)、纯化的大豆苷元(200 mg/kg饮食)、染料木黄酮+大豆苷元(各100 mg/kg饮食)、含有正常水平的大豆异黄酮的SPI(SPI-n)或耗尽大豆异黄酮的SPI(SPI-d)。在动物开始食用实验饮食后1周,通过引入7,12-二甲基苯并[a]蒽(DMBA)诱导乳腺癌。在研究结束时(DMBA处理后120天),在肿瘤发生率或存活率方面,六组之间没有发现显著差异,染料木素或染料木素+大豆苷元组的肿瘤多样性也没有显著降低。然而,相对于对照组,大豆黄酮和SPI-n组的肿瘤多样性降低了32%(P < 0.05)。最有效的饮食是SPI-d,其相对于对照产生了50%的肿瘤多样性降低(P < 0.01)。SPI-d组与大豆苷元组、SPI-n组之间差异不显著。中位肿瘤潜伏期从对照组的53天增加到大豆苷元组的68天和SPI-d组的72天,但这些差异没有统计学意义。这些结果表明,大豆黄酮和SPI(具有正常或低水平的大豆黄酮)是DMBA诱导的成年大鼠乳腺肿瘤的有效抑制剂。
There are conflicting reports on the effect of soy and its components on mammary carcinogenesis in adult-female rats, mainly because of different rodent models that are used in chemoprevention studies. The present study was undertaken to compare the tumor-preventative effects of soy protein isolate (SPI) and two of its isoflavones in a "standard" model that had been used for the identification of many chemopreventive agents. Six groups of female Sprague-Dawley rats were provided with modified corn-starch AIN-76A diets supplemented as follows: no additional agents (control), purified genistein (200 mg/kg diet), purified daidzein (200 mg/kg diet), genistein + daidzein (100 mg/kg diet each), SPI containing normal levels of isoflavones (SPI-n), or SPI depleted of isoflavones (SPI-d). Mammary carcinomas were induced by 7,12-dimethylbenz[a]anthracene (DMBA) introduced 1 wk after the animals began consuming the experimental diets. At the end of the study (120 days after DMBA treatment), no significant differences were found among the six groups with respect to tumor incidence or survival, nor was there a significant reduction in tumor multiplicity in the genistein or genistein + daidzein group. However, there was a 32% reduction in tumor multiplicity in the daidzein and SPI-n groups relative to the control group (P < 0.05). The most effective diet was SPI-d, which produced a 50% reduction in tumor multiplicity relative to the control (P < 0.01). The difference between the SPI-d group and the daidzein or SPI-n group was not significant. Median tumor latency was increased from 53 days in the control group to 68 days in the daidzein group and to 72 days in the SPI-d group, but these differences were not statistically significant. These results show that daidzein and SPI (with normal or low levels of isoflavones) are effective inhibitors of DMBA-induced mammary tumors in adult rats.