title: Mitochondrial decay is involved in BaP-induced cervical damage.
abstract: Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon and a potent inducer of carcinogenesis. Many studies have reported that the carcinogenic effects of BaP might be due to its intermediate metabolites and to reactive oxygen species (ROS) that cause oxidative damage to the cells. However, the mechanisms of BaP-induced oxidative damage in cervical tissue are still not clear. We studied these mechanisms in female ICR mice treated with BaP either orally or intraperitoneally by measuring (1) several general biomarkers of oxidative stress in serum, (2) mitochondrial function in the cervix, and (3) the morphology of mitochondria in cervical tissue. BaP treatment (1) significantly lowered levels of vitamins A, C, and E and of glutathione; (2) reduced activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferases; and (3) significantly increased lipid peroxidation levels. In addition, significant increases in the levels of superoxide anion, hydrogen peroxide, and hydroxyl radical were observed. These results were confirmed by morphological changes in mitochondria and by decreases in membrane potential levels and in succinate dehydrogenase and malate dehydrogenase activities. The changes in these biomarkers and mitochondrial damage were BaP-dose-dependent and eventually induced both cell apoptosis and necrosis in cervical tissue. As mitochondria are the major sites of ROS generation, these findings show that mitochondrial decay greatly contributes to BaP-induced cervical damage.
authors.affiliation: Institute of Cancer Research, Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, China. gaomeili@mail.xjtu.edu.cn
authors.forename: Meili
authors.initials: M
authors.lastname: Gao
authors.forename: Jiangang
authors.initials: J
authors.lastname: Long
authors.forename: Yongfei
authors.initials: Y
authors.lastname: Li
authors.forename: Walayat
authors.initials: W
authors.lastname: Shah
authors.forename: Ling
authors.initials: L
authors.lastname: Fu
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
authors.forename: Yili
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002584:Cervix Uteri / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D009153:Mutagens / Q000633:toxicity; D009336:Necrosis; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D002577:Uterine Cervical Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology
chemical_list: D009153:Mutagens; D017382:Reactive Oxygen Species; D001564:Benzo(a)pyrene; D008315:Malondialdehyde