Carcinogenic potential of ovulatory genotoxicity.
Ovulation is a rate-limiting event for the perpetuation of a species; unfortunately, it imparts a cancer risk. Reactive oxidants generated during the mechanics of ovulatory follicular rupture damage the DNA of ovarian surface epithelial cells that are located within a limited diffusion radius. Those cells that survive the trauma of ovulation, along the margins of a ruptured follicle, proliferate and migrate to reconcile the discontinuity within the ovarian epithelium created at the site of oocyte release. It is conceivable that clonal expansion of an ovarian surface epithelial cell with unrepaired DNA, but not committed to death, could be an initiating factor in the etiology of common ovarian cancer. In fact, the majority of cancers of the ovary are derived from the surface epithelium; and circumstances that avert ovulation (oral contraceptive use, pregnancy/lactation) protect against ovarian adenocarcinoma. Not surprisingly, the genotoxic potential of ovulation is exacerbated by malfunctions in tumor suppressor/cell-cycle arrest and base-excision repair mechanisms. Recent experimental evidence indicates that vitamin E and progesterone protect against ovarian metaplasia by negating the oxidative stress of ovulation and by enhancing the repair capacity (genomic integrity) of the surface epithelium, respectively. Ovarian cancer of surface epithelial origin is a deadly insidious disease because it characteristically remains asymptomatic until it has metastasized throughout the abdominal cavity; therefore, prevention is a high priority.
Murdoch
William J
WJ
Department of Animal Science and Reproductive Biology Program, University of Wyoming, Laramie, 82071, USA. wmurdoch@uwyo.edu
D000230:Adenocarcinoma / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D003271:Contraceptive Agents, Female / Q000494:pharmacology; D004249:DNA Damage; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D007774:Lactation; D010051:Ovarian Neoplasms / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D010060:Ovulation / Q000502:physiology*; D018384:Oxidative Stress; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D003271:Contraceptive Agents, Female; D014810:Vitamin E; D011374:Progesterone