Rapid induction of mammary cancer by repeated subcutaneous injection of the trans-3,4-dihydrodiol of 7,12-dimethylbenz[a]anthracene in the female Sprague-Dawley rat.

Rapid induction of mammary cancer by repeated subcutaneous injection of the trans-3,4-dihydrodiol of 7,12-dimethylbenz[a]anthracene in the female Sprague-Dawley rat.
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通过在雌性 Sprague-Dawley 大鼠中重复皮下注射 7,12-二甲基苯并[a]蒽的反式 3,4-二氢二醇快速诱导乳腺癌。

DOI:
10.1016/j.canlet.2004.07.039
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发表时间:
2005
期刊:
Cancer letters.
影响因子:
--
通讯作者:
Flesher,JamesW
Flesher,JamesW
中科院分区:
--
文献类型:
--
作者:
Horn,Jamie;Lehner,AndreasF;Flesher,JamesW

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在50日龄Sprague-Dawley雌性大鼠中,单次经口给予20 mg剂量的7,12-二甲基苯并[a]蒽定期并快速诱发乳腺癌[实验性白血病和乳腺癌,1979,第74页]。已经提出了7,12-二甲基苯并[a]蒽诱导乳腺癌的几种机制,并且各种衍生物被认为是这种烃的可能的接近或最终亲电和致癌形式。在这里,我们表明,7,12-二甲基苯并[a]蒽-反式-3,4-二氢二醇通过重复皮下注射在注射部位无恶性肿瘤的雌性Sprague-Dawley大鼠中的高比例快速诱导乳腺癌,而其更脂溶性的二乙酸酯衍生物除了远端乳腺癌外还诱导注射部位肉瘤。相比之下,重复皮下注射7,12-二甲基苯并[a]蒽及其7-内消旋醛衍生物在大多数(如果不是全部)大鼠和少数乳腺癌中诱导皮下肉瘤。
The oral administration of a single 20mg dose of 7,12-dimethylbenz[a]anthracene regularly and rapidly induces mammary cancer in 50 day-old Sprague–Dawley female rats [Experimental Leukemia and Mammary Cancer, 1979, p. 74]. Several mechanisms by which 7,12-dimethylbenz[a]anthracene induces mammary cancer have been proposed and various derivatives have been implicated as possible proximate or ultimate electrophilic and carcinogenic forms of this hydrocarbon. Here we show that 7,12-dimethylbenz[a]anthracene-trans-3,4-dihydrodiol rapidly induces mammary cancer by repeated subcutaneous injection in a high proportion of female Sprague–Dawley rats without malignancies at the site of injection, whereas its more lipid soluble diacetate derivative induced injection site sarcomas in addition to distal mammary cancers. By contrast, repeated subcutaneous injection of 7,12-dimethylbenz[a]anthracene and its 7-meso-aldehyde derivative induced subcutaneous sarcoma in most, if not all, rats and a few mammary cancers.
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