Ovulation-induced DNA damage in ovarian surface epithelial cells of ewes: Prospective regulatory mechanisms of repair/survival and apoptosis

Oxidative base (8-oxoguanine) damage, DNA fragmentation, and apoptosis occu rred among ovarian surface epithelial cells within the formative site of ov ulation in sheep. The incidence of 8-oxoguanine adducts in surviving antiap optotic Bcl-2/base excision repair polymerase beta -positive cells at the m argins 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 avert ed by ovulation blockade with indomethacin. Progesterone enhanced the biosy nthesis of polymerase beta in ovarian surface epithelial cells exposed in v itro to a sublethal concentration of H2O2. Ovulation is a putative etiologi cal factor in common epithelial ovarian cancer. A genetically altered proge nitor cell, with unrepaired DNA, but not committed to death, could give ris e to a transformed phenotype that is hence propagated upon healing of the o vulatory wound; it appears that this incongruity is normally reconciled by up-regulation of the base excision repair pathway during the ensuing luteal phase.