Tamoxifen induces rapid, reversible atrophy, and metaplasia in mouse stomach.

Tamoxifen induces rapid, reversible atrophy, and metaplasia in mouse stomach.
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DOI:
10.1053/j.gastro.2011.09.050
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发表时间:
2012-01
期刊:
影响因子:
29.4
通讯作者:
Mills JC
Mills JC
中科院分区:
医学1区
文献类型:
--
作者:
Huh WJ;Khurana SS;Geahlen JH;Kohli K;Waller RA;Mills JC

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他莫昔芬是一种选择性雌激素受体调节剂,广泛用于研究和临床患者。我们发现,用单次≥ 3 mg/20 g体重剂量的他莫昔芬治疗正常小鼠,在3天内导致> 90%的所有胃壁细胞凋亡和酶原主细胞化生。值得注意的是,胃组织学在3周内恢复到几乎正常。他莫昔芬毒性发生口服和腹腔内给药,在两种性别,在多个菌株,并不依赖于雌激素,虽然酸分泌抑制是部分保护。因此,显著的胃毒性是迄今为止未被认识到的他莫昔芬副作用。
Tamoxifen, a selective estrogen receptor modulator, is widely used in research and clinically in patients. We find that treatment of normal mice with a single ≥ 3mg/20g body weight dose of tamoxifen leads to apoptosis of > 90% of all gastric parietal cells and metaplasia of zymogenic chief cells within 3 days. Remarkably, gastric histology returns to nearly normal by 3 weeks. Tamoxifen toxicity occurs by oral and intraperitoneal administration, in both sexes, in multiple strains, and does not depend on estrogen, though acid secretion inhibition is partially protective. Thus, substantial gastric toxicity is a heretofore unappreciated tamoxifen side effect.
胃上皮祖细胞生态位和酶原(主要)细胞谱系的分化。
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