Murdoch William J, Van Kirk Edward A, Alexander Brenda M
Department of Animal Science and Reproductive Biology Program, 1000 E. University Avenue, University of Wyoming, Laramie, Wyoming 82071, USA.
Exp Biol Med (Maywood). 2005 Jun;230(6):429-33. doi: 10.1177/15353702-0323006-11.
A cause-effect relationship between ovulation and common (surface) epithelial ovarian cancer has been suspected for many years. The ovarian surface epithelium apparently becomes exposed to genotoxins that are generated during the ovulatory process. Intensive egg-laying hens readily develop ovarian carcinomatosis. Indeed, elevated levels of potentially mutagenic 8-oxo-guanine adducts were detected in avian ovarian epithelial cells isolated from the apical surfaces and perimeters of pre-and postovulatory follicles, respectively. Internucleosomal DNA fragmentation indicative of apoptosis was evident in ovarian surface epithelial cells associated with the formative site of ovulation (stigma line) and regressive ruptured follicles. It is conceivable that a genetically altered progenitor cell with unrepaired DNA but not committed to death (i.e., a unifocal "escape") could give rise to a transformed phenotype. Hence, the high rate of ovarian cancer in egg-laying hens could be the consequence of genomic damages to the ovarian surface epithelium associated with incessant ovulations, thereby increasing the likelihood of mutation and clonal expansion.
多年来,人们一直怀疑排卵与常见的(表面)上皮性卵巢癌之间存在因果关系。卵巢表面上皮显然会接触到排卵过程中产生的基因毒素。产蛋频繁的母鸡很容易患上卵巢癌。事实上,分别从排卵前和排卵后卵泡的顶端表面和周边分离出的禽类卵巢上皮细胞中,检测到了潜在诱变的8-氧代鸟嘌呤加合物水平升高。在与排卵形成部位(柱头线)和退化破裂卵泡相关的卵巢表面上皮细胞中,明显存在指示凋亡的核小体间DNA片段化。可以想象,一个具有未修复DNA但未走向死亡的基因改变的祖细胞(即单灶性“逃逸”)可能会产生转化表型。因此,产蛋母鸡卵巢癌的高发病率可能是由于与持续排卵相关的卵巢表面上皮基因组损伤的结果,从而增加了突变和克隆扩增的可能性。