Document Detail

Autophagy is a cell self-protective mechanism against arsenic-induced cell transfomation.
MedLine Citation:
PMID:  22869613     Owner:  NLM     Status:  Publisher    
Long-term exposure to arsenic increases the incidence of human cancers, such as skin, lung, colon and rectal cancer. The mechanism for arsenic-induced tumorigenesis is still not clear. It is generally believed that DNA damage and genomic instability, generated by arsenic-promoted oxidative stress, are the causes of this process. The major sources of reactive oxygen species (ROS) are arsenic-damaged mitochondria. Autophagy is a catabolic process functioning in turnover of long-lived proteins and dysfunctional organelles such as mitochondria. Defects of autophagy under stress conditions promote genomic instability and increase the risk of tumorigenesis. In the present study using a human bronchial epithelial cell line, BEAS-2B cells, we investigated the role of autophagy in arsenic-induced cell transformation, an important step in arsenic tumorigenesis. Our results show that long-term arsenic exposure induces BEAS-2B cell transformation accompanied with increased ROS generation and autophagy activation. However, the patterns for ROS and autophagy alteration are different. Arsenic exposure generated a prolonged and steady increase of ROS levels, while the activation of autophagy, after an initial boost by arsenic administration, decreases gradually in response to long-term arsenic exposure, although the activity is still higher than a non-treated control. Further stimulation of autophagy increases mitochondria turnover and decreases ROS generation as well as arsenic-induced cell transformation. In contrast, inhibition of autophagy activity decreases mitochondria turnover and enhances arsenic-induced ROS generation and cell transformation. In addition, the mTOR signaling pathway is involved in arsenic-mediated autophagy activation. Our results suggest that autophagy is a cell self-protective mechanism against arsenic-induced cell transformation.
Tao Zhang; Yuanlin Qi; Mingjun Liao; Mei Xu; Kimberly Bower; Jacqueline Frank; Han-Ming Shen; Jia Luo; Xianglin Shi; Gang Chen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-5
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  -     ISSN:  1096-0929     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
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