title: Low Concentration of Exogenous Carbon Monoxide Modulates Radiation-Induced Bystander Effect in Mammalian Cell Cluster Model.
abstract: During radiotherapy procedures, radiation-induced bystander effect (RIBE) can potentially lead to genetic hazards to normal tissues surrounding the targeted regions. Previous studies showed that RIBE intensities in cell cluster models were much higher than those in monolayer cultured cell models. On the other hand, low-concentration carbon monoxide (CO) was previously shown to exert biological functions via binding to the heme domain of proteins and then modulating various signaling pathways. In relation, our previous studies showed that exogenous CO generated by the CO releasing molecule, tricarbonyldichlororuthenium (CORM-2), at a relatively low concentration (20 µM), effectively attenuated the formation of RIBE-induced DNA double-strand breaks (DSB) and micronucleus (MN). In the present work, we further investigated the capability of a low concentration of exogenous CO (CORM-2) of attenuating or inhibiting RIBE in a mixed-cell cluster model. Our results showed that CO (CORM-2) with a low concentration of 30 µM could effectively suppress RIBE-induced DSB (p53 binding protein 1, p53BP1), MN formation and cell proliferation in bystander cells but not irradiated cells via modulating the inducible nitric oxide synthase (iNOS) andcyclooxygenase-2 (COX-2). The results can help mitigate RIBE-induced hazards during radiotherapy procedures.
authors.affiliation: Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China. 18256986803@163.com.
authors.forename: Wenqing
authors.initials: W
authors.lastname: Wu
authors.affiliation: Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China. niell@cmpt.ac.cn.
authors.forename: Lili
authors.initials: L
authors.lastname: Nie
authors.affiliation: Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China. peter.yu@cityu.edu.hk.|Department of Physics and Materials Science, City University of Hong Kong, TatChee Avenue, Kowloon Tong, Hong Kong, China. peter.yu@cityu.edu.hk.
authors.forename: K N
authors.initials: KN
authors.lastname: Yu
authors.affiliation: Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China. ljw@ipp.ac.cn.|Institute of Technical Biology & Agricultural Engineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China. ljw@ipp.ac.cn.
authors.forename: Lijun
authors.initials: L
authors.lastname: Wu
authors.affiliation: Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China. gckongpz@163.com.
authors.forename: Peizhong
authors.initials: P
authors.lastname: Kong
authors.affiliation: Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China. lingzhibao@hfcas.ac.cn.
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Bao
authors.affiliation: Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China. c3024034@163.com.
authors.forename: Guodong
authors.initials: G
authors.lastname: Chen
authors.affiliation: Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China. yhr2853@163.com.
authors.forename: Haoran
authors.initials: H
authors.lastname: Yang
authors.affiliation: Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China. hanw@hfcas.ac.cn.|Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Suzhou 215000, China. hanw@hfcas.ac.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
mesh_terms: D000818:Animals; D024201:Bystander Effect / Q000187:drug effects* / Q000528:radiation effects*; D016466:CHO Cells; D002248:Carbon Monoxide / Q000494:pharmacology*; D002449:Cell Aggregation / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D003412:Cricetulus; D051546:Cyclooxygenase 2 / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects / Q000528:radiation effects; D008954:Models, Biological; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D011827:Radiation; D000071857:Tumor Suppressor p53-Binding Protein 1 / Q000378:metabolism; D014965:X-Rays
chemical_list: D000071857:Tumor Suppressor p53-Binding Protein 1; D002248:Carbon Monoxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2
keywords: cell cluster model; cyclooxygenase-2; inducible nitric oxide synthase; low centration of carbon monoxide; radiation-induced bystander effect