Charles River Sprague Dawley rats lack early age-dependent susceptibility to DMBA-induced mammary carcinogenesis.
Charles River Sprague Dawley rats lack early age-dependent susceptibility to DMBA-induced mammary carcinogenesis.
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查尔斯河Sprague Dawley大鼠缺乏早期依赖性DMBA诱导的乳腺癌作用的敏感性。
DOI：
10.7150/ijbs.3.408
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发表时间：
2007-10-04
影响因子：
9.2
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中科院分区：
文献类型：
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乳腺的发育阶段影响其对与癌变相关的起始事件的易感性。对乳腺癌发生的“易感窗口”被经典地定义为青春期早期的时间，此时乳腺形态对起始事件最敏感。当在该“窗口”内给药时，以单次口服剂量给予聚芳烃7，12-二甲基苯并（a）蒽（DMBA）产生最大的乳腺肿瘤形成。我们检查了Charles River Sprague道利CDR IGS出生后前100天内DMBA处理的乳腺、前驱病变和未受累乳腺上皮的形态学。我们的目标是确定DMBA剂量，在该剂量下，50%的大鼠（IC 50）在给药后三个月内发生原位癌（CIS）。在这里，我们证明，而不是经典的U形剂量曲线，其中有最大的敏感性DMBA在50天，有一个随着年龄的增加，在CDR IGS大鼠的敏感性程度。此外，我们报告称，溶剂处理的动物在没有任何已知引发剂的情况下发生了乳腺CIS，100天的处女动物表现出泌乳变化，与DMBA暴露或剂量无关。最后，我们证明了这一品系的处女雌性大鼠具有独立于乳腺分化水平的垂体催乳素免疫反应性升高。我们得出结论，该品系的Charles River Sprague道利大鼠具有催乳素诱导的垂体刺激，因此，不存在乳腺肿瘤发生的易感窗口。
Developmental stages of mammary glands influence their susceptibility to initiating events related to carcinogenesis. The “window of susceptibility” to mammary carcinogenesis is classically defined as the time in early puberty when the mammary gland morphology is most sensitive to initiation events. Administration of the polyaromatic hydrocarbon, 7,12-dimethylbenz(a)anthracene (DMBA), in a single oral dose yields maximal mammary tumor formation when administered in this “window”. We examined the DMBA treated mammary glands, precursor lesions, and morphology of the uninvolved mammary epithelium for the first 100 days of life for Charles River Sprague Dawley CDR IGS. Our goal was to determine the DMBA dose at which 50% of the rats (IC50) developed carcinoma in situ (CIS) within three months of dosing. Here we demonstrate, rather than the classical U-shaped dose curve in which there is maximum sensitivity for DMBA at 50 days, there is an increasing degree of sensitivity with age in the CDR IGS rat. Additionally, we report that vehicle-treated animals developed mammary CIS without any known initiator, and 100 day virgin animals demonstrated lactational changes, independent of DMBA exposure or dose. Lastly, we demonstrate this strain of virgin female rats has elevated pituitary prolactin immunoreactivity independent of the level of mammary differentiation. We conclude this strain of Charles River Sprague Dawley rats has prolactin-induced pituitary stimulation, and therefore, the window of susceptibility for mammary tumorigenesis is absent.