Oxidative damage to DNA of ovarian surface epithelial cells affected by ovulation: Carcinogenic implication and chemoprevention
Oxidative damage to DNA of ovarian surface epithelial cells affected by ovulation: Carcinogenic implication and chemoprevention
复制标题
DOI：
10.1177/153537020422900613
复制
发表时间：
2004-06-01
影响因子：
3.2
通讯作者：
Martinchick, JF
中科院分区：
文献类型：
--
作者：
Murdoch, WJ;Martinchick, JF
大多数卵巢癌被认为起源于受排卵干扰的表面上皮细胞。注定要排卵的卵泡的生长使其与卵巢上皮对接。因此，卵巢表面细胞在有限的扩散半径内暴露在排卵过程中产生的炎症介质和活性氧化剂中。覆盖在卵泡破裂形成部位的细胞会遭受不可修复的损伤并发生凋亡。在排泄后绵羊和人类卵泡周围的(存活的)细胞中检测到了潜在的突变8-氧鸟嘌呤修饰。可以想象，带有未修复DNA的细胞的克隆性扩张，但不会导致死亡，可能是恶性肿瘤病因中的一个启动因素，因为增殖性排卵创伤修复反应可能会传播突变。由于卵巢癌侵袭性疾病患者的预后如此之差，而且早期发现已被证明是难以捉摸的，因此探索前瞻性的化学预防方法是当务之急。维生素E可预防排卵对绵羊卵巢上皮细胞的氧化碱基损伤，恶鸟苷加合物持续存在，CA-125(一种化生转化的表型)在排卵困难的细胞培养中表达，其中P53的合成受到抑制。维生素E否定了这一反应。在服用维生素的母羊中，卵巢的周期性和受精性没有改变。补充抗氧化剂对“排卵期”的卵巢癌高危人群(例如，由于肿瘤抑制功能障碍)具有预防作用。
The majority of cancers of the ovary are thought to originate from a surface epithelial cell perturbed by ovulation. Outgrowth of a follicle destined to ovulate brings it into apposition with the ovarian epithelium. Ovarian surface cells are consequently exposed, within a limited diffusion radius, to inflammatory agents and reactive oxidants generated during periovulatory processes. Cells that overlie the formative site of follicular rupture suffer irreparable damages and undergo apoptosis. Potentially mutagenic 8-oxoguanine modifications were detected in (surviving) cells circumjacent to postovulatory ovine and human follicles. It is conceivable that clonal expansion of a cell with unrepaired DNA, but not committed to death, could be an initiating factor in the etiology of malignancy, insofar as proliferative ovulatory wound-repair responses may propagate mutations. Since the prognosis for ovarian cancer patients with invasive disease is so poor, and early detection has proven elusive, it is imperative that prospective methods of chemoprevention be explored. Ovulation-induced oxidative base damages to the ovarian epithelium of ewes were prevented by vitamin E. Oxoguanine adducts persisted and CA-125 (a phenotype of metaplastic transformation) was expressed in cultures of cells that were distressed by ovulation in which p53 synthesis was inhibited. Vitamin E negated this reaction. Ovarian cyclicity and fertility were not altered in vitamin-treated ewes. A prophylactic benefit of a supplemental antioxidant is suggested in "ovulating" individuals designated at risk (e.g., due to a tumor suppressor malfunction) for the development of ovarian cancer.