Low doses of arsenic, via perturbing p53, promotes tumorigenesis.
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.
['Ganapathy|Suthakar|S|', 'Li|Ping|P|', 'Fagman|Johan|J|', 'Yu|Tianqi|T|', 'Lafontant|Jean|J|', 'Zhang|Guojun|G|', 'Chen|Changyan|C|']
D001151:Arsenic D063646:Carcinogenesis D002273:Carcinogens D002460:Cell Line D059865:Endoplasmic Reticulum Stress D006801:Humans D015603:Keratinocytes D017382:Reactive Oxygen Species D016159:Tumor Suppressor Protein p53 D056811:Unfolded Protein Response
Arsenic p53 Tumorigenesis ER stress