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Regular Article |
a Department of Animal Science and Reproductive Biology Program, University of Wyoming, Laramie, Wyoming 82071
ABSTRACT
Oxidative base (8-oxoguanine) damage, DNA fragmentation, and apoptosis occurred among ovarian surface epithelial cells within the formative site of ovulation in sheep. The incidence of 8-oxoguanine adducts in surviving antiapoptotic Bcl-2/base excision repair polymerase ß-positive cells at the margins of ruptured follicles (which avoid the focal point of the ovulatory assault) was intermediate between apoptotic and outlying healthy epithelium. Cells containing perturbations to DNA expressed the tumor suppressor p53. Localized reactions of DNA injury and programmed cellular death were averted by ovulation blockade with indomethacin. Progesterone enhanced the biosynthesis of polymerase ß in ovarian surface epithelial cells exposed in vitro to a sublethal concentration of H2O2. Ovulation is a putative etiological factor in common epithelial ovarian cancer. A genetically altered progenitor cell, with unrepaired DNA, but not committed to death, could give rise to a transformed phenotype that is hence propagated upon healing of the ovulatory wound; it appears that this incongruity is normally reconciled by up-regulation of the base excision repair pathway during the ensuing luteal phase.
1 Supported by U.S. Department of Agriculture-NRI grant 95-37203-2131.
2 Correspondence: W.J. Murdoch, Department of Animal Science, P.O. Box 3684, University of Wyoming, Laramie, WY 82071. FAX: 307 766 2355; wmurdoch{at}uwyo.edu
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