他莫昔芬可减少 DMBA 实验性毒物和环磷酰胺及阿霉素化疗药物引起的大鼠卵巢卵泡丢失。
Tamoxifen decreases ovarian follicular loss from experimental toxicant DMBA and chemotherapy agents cyclophosphamide and doxorubicin in the rat.
机构信息
Breast Cancer Prevention Center, University of Kansas Medical Center, Kansas City, KS 66160, USA.
出版信息
J Assist Reprod Genet. 2010 Nov;27(11):591-7. doi: 10.1007/s10815-010-9463-y. Epub 2010 Aug 14.
Abstract
INTRODUCTION
we serendipitously observed a protective effect of tamoxifen against depletion of ovarian follicles by 7,12-dimethylbenzanthracene (DMBA), a chemical carcinogen, during a cancer prevention study. Such ovarian protection is being sought as an alternative approach to fertility preservation in human cancer patients.
METHODS
rats received tamoxifen (0, 1 mg or 2.5 mg/kg/d) and DMBA (0, 1, 2 mg/kg/wk) or cyclophosphamide (0, 35, 50 mg/kg/wk). Ovarian follicles were quantified and effects on fertility and litter size were tested. Cultured oocytes were exposed to chemotherapy drug doxorubicin, with or without 4-hydroxytamoxifen (4HT).
RESULTS
DMBA and cyclophosphamide decreased the number of primordial and total follicles, and this reduction was prevented by tamoxifen. Cyclophosphamide tended to reduce fertility and lessened neonatal survival. Tamoxifen reversed these defects. Doxorubicin caused oocyte fragmentation which was prevented by 4HT.
CONCLUSIONS
tamoxifen decreases follicle loss and improves reproductive function following exposure to ovarian toxicants including chemotherapy drugs in the female rat.
摘要
简介
在一项癌症预防研究中，我们偶然观察到他莫昔芬对 7,12-二甲基苯并蒽（DMBA）这种化学致癌剂引起的卵巢卵泡耗竭具有保护作用。这种卵巢保护作用正被作为一种替代方法来保留人类癌症患者的生育能力。
方法
大鼠接受他莫昔芬（0、1 毫克或 2.5 毫克/千克/天）和 DMBA（0、1、2 毫克/千克/周）或环磷酰胺（0、35、50 毫克/千克/周）。定量检测卵巢卵泡数，并测试其对生育力和产仔数的影响。将培养的卵母细胞暴露于化疗药物阿霉素中，同时或不使用 4-羟基他莫昔芬（4HT）。
结果
DMBA 和环磷酰胺减少了原始卵泡和总卵泡的数量，而他莫昔芬则阻止了这种减少。环磷酰胺往往会降低生育力并降低新生儿存活率。他莫昔芬逆转了这些缺陷。阿霉素导致卵母细胞碎片化，而 4HT 可防止这种碎片化。
结论
他莫昔芬可减少雌性大鼠暴露于卵巢毒物（包括化疗药物）后卵泡的丢失，并改善生殖功能。
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