title: Low doses of arsenic, via perturbing p53, promotes tumorigenesis.
abstract: In drinking water and in workplace or living environments, low doses of arsenic can exist and operate as a potent carcinogen. Due to insufficient understanding and information on the pervasiveness of environmental exposures to arsenic, there is an urgent need to elucidate the underlying molecular mechanisms of arsenic regarding its carcinogenic effect on human health. In this study, we demonstrate that low doses of arsenic exposure mitigate or mask p53 function and further perturb intracellular redox state, which triggers persistent endoplasmic reticulum (ER) stress and activates UPR (unfolded protein response), leading to transformation or tumorigenesis. Thus, the results suggest that low doses of arsenic exposure, through attenuating p53-regulated tumor suppressive function, change the state of intracellular redox and create a microenvironment for tumorigenesis. Our study also provides the information for designing more effective strategies to prevent or treat human cancers initiated by arsenic exposure.
authors.affiliation: Center for Drug Development, Northeastern University, Boston, USA. Electronic address: s.ganapathy@neu.edu.
authors.forename: Suthakar
authors.initials: S
authors.lastname: Ganapathy
authors.affiliation: The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China; The Institute of Clinic Sciences, Sahlgrenska Academy, Gothenburg, Sweden.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: The Institute of Clinic Sciences, Sahlgrenska Academy, Gothenburg, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Fagman
authors.affiliation: Center for Drug Development, Northeastern University, Boston, USA.
authors.forename: Tianqi
authors.initials: T
authors.lastname: Yu
authors.affiliation: Center for Drug Development, Northeastern University, Boston, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Lafontant
authors.affiliation: The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Center for Drug Development, Northeastern University, Boston, USA; The Institute of Clinic Sciences, Sahlgrenska Academy, Gothenburg, Sweden.
authors.forename: Changyan
authors.initials: C
authors.lastname: Chen
mesh_terms: D001151:Arsenic / Q000633:toxicity*; D063646:Carcinogenesis / Q000187:drug effects* / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D056811:Unfolded Protein Response / Q000187:drug effects
chemical_list: D002273:Carcinogens; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D001151:Arsenic
keywords: Arsenic; ER stress; Tumorigenesis; p53