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Mutagenicity of PFOA in Mammalian Cells: Role of Mitochondria-Dependent Reactive Oxygen Species.
MedLine Citation:
PMID:  21194205     Owner:  NLM     Status:  Publisher    
Mutagenicity is often a prerequisite to the development of malignancy. Evidences have shown that exposure to perfluorooctanoic acid (PFOA) results in various cancer inductions. However, whether any mutagenic base exists is still puzzling. In the present study, we exposed exponentially growing A(L) cells to PFOA and assayed the cells for survival, mutation induction, and caspase-3/7, -9 activities. Mitochondrial-DNA deficient human-hamster hybrid (ρ(0) A(L)) cells and reactive oxygen species (ROS) inhibitor were used to elucidate the possible mechanism. Our results showed that treatment of A(L) cells with PFOA for 16 days induced significant mutagenic effects together with the increment of ROS, superoxide anions (O(2)(.-)), and nitrogen oxide (NO) levels, while treatment of ρ(0) A(L) cells did not have much change. Concurrent treatment of A(L) cells with ROS inhibitor significantly decreased the mutagenic potential of PFOA. In addition, caspase activities in A(L) cells were increased by PFOA exposure and suppressed by ROS/RNS (reactive oxygen/nitrogen species) inhibitors. Our results suggest that exposure to PFOA lead to mutagenicity induction in A(L) cells, and mitochondria-dependent ROS plays an important role in this process. This provides a direct base for PFOA mediated cancer induction.
Guoping Zhao; Jun Wang; Xiaofei Wang; Shaopeng Chen; Ye Zhao; Feng Gu; An Xu; Lijun Wu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-12-31
Journal Detail:
Title:  Environmental science & technology     Volume:  -     ISSN:  1520-5851     ISO Abbreviation:  -     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2011-1-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0213155     Medline TA:  Environ Sci Technol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences , Hefei 230031, Anhui, PR China.
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