title: Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells.
abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H2O2) and superoxide dismutase 2 (SOD2, antioxidant against O2(-)) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous report. The present study has also shown that the arsenic-transformed cells acquired apoptosis resistance. The inhibition of catalase to increase ROS level restored apoptosis capability of arsenic-transformed BEAS-2B cells, further showing that ROS levels are low in these cells. The apoptosis resistance due to the low ROS levels may increase cells proliferation, providing a favorable environment for tumorigenesis of arsenic-transformed cells.
authors.affiliation: Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536, USA. Electronic address: zhuo.zhang@uky.edu.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Poyil
authors.initials: P
authors.lastname: Pratheeshkumar
authors.affiliation: Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Budhraja
authors.affiliation: Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Young-Ok
authors.initials: YO
authors.lastname: Son
authors.affiliation: Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Donghern
authors.initials: D
authors.lastname: Kim
authors.affiliation: Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Shi
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001151:Arsenic / Q000633:toxicity*; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002374:Catalase / Q000037:antagonists & inhibitors; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D002274:Carcinogens, Environmental; D017382:Reactive Oxygen Species; D002374:Catalase; D001151:Arsenic
keywords: Antioxidant enzymes; Arsenic; Cell transformation; Reactive oxygen species