Mutagenic, surviving and tumorigenic effects of follicular fluid in the context of p53 loss: initiation of fimbria carcinogenesis.

摘要: Ovulation is the strongest risk factor for ovarian high-grade serous carcinoma (HGSC) that largely originates from fallopian tube fimbriae and always carries loss-of-function mutations of TP53 in both early late lesions. Mature follicle contains high level reactive oxygen species (ROS). When released ovulation, follicular fluid (FF) bathes may lead to DNA double-strand break (DSB) neoplastic transformation. In this study, we examined mutagenic tumorigenic activities human pre-ovulatory FFs. A subset (6/11) FFs was found with levels ROS whereas antioxidant capacities were indifferent. These ROS(high) induced intracellular DSBs secretory cell population epithelium. p53 Rb turned down, FF-exposed cells overcame apoptosis expanded carrying DSB. The cancer initiation promotion effects FF further recapitulated Trp53 (-/-) mice. introduced into mammary fat pad, but not ROS(low) early-onset B-cell lymphoma. Cotreatment physiological concentration melatonin, a potent antioxidant, ameliorated effect vitro vivo. study revealed mitogens mature follicles could initiate transformation fimbria epithelium context loss melatonin preventive agent.