title: Conditioned medium from actinomycin D-treated apoptotic cells induces mitochondria-dependent apoptosis in bystander cells.
abstract: Chemical-induced bystander effects have been known for several years, but the underlying mechanism is still seldom investigated. Previous researchers have found that mitomycin C and phleomycin induced micronuclei in bystander cells the same as in exposed cells. We previously demonstrated the ability of actinomycin D (ACTD) to induce bystander effects in normal Chinese hamster fibroblast V79 cells and found that conditioned medium (CM) obtained from ACTD-exposed apoptotic cells induced apoptosis in bystander cells. The present study further explores the probable mechanism of apoptosis in bystander cells. The main findings of this study are: (1) ACTD-treated CM induced apoptosis in bystander cells in a time-dependent manner, which was confirmed with morphological changes. (2) ACTD-treated CM increased the mRNA and protein levels of pro-apoptotic p53 and Bax, whereas it decreased those of anti-apoptotic Bcl-2 in bystander cells; these were all time-dependent effects. Reactive oxygen species (ROS) were also involved in apoptosis of bystander cells. (3) ACTD-treated CM reduced mitochondria membrane potential and induced cytochrome c release. (4) ACTD-treated CM induced G1 cell phase arrest, which may be another response in bystander cells when cultured with CM. These results suggest that chemical-treated CM induces p53-Bcl-2/Bax-cytochrome c signaling (i.e., mitochondria pathway)-dependent apoptosis in bystander cells, which is a kinetic response.
authors.affiliation: Department of Toxicology, School of Public Health, China Medical University, Shenyang 110001, PR China.
authors.forename: Cuihong
authors.initials: C
authors.lastname: Jin
authors.forename: Shengwen
authors.initials: S
authors.lastname: Wu
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Lu
authors.forename: Qiufang
authors.initials: Q
authors.lastname: Liu
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhang
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yang
authors.forename: Qi
authors.initials: Q
authors.lastname: Xi
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D024201:Bystander Effect / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D017077:Culture Media, Conditioned; D045304:Cytochromes c / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017077:Culture Media, Conditioned; D017382:Reactive Oxygen Species; D003609:Dactinomycin; D045304:Cytochromes c