title: Mutagenicity of PFOA in mammalian cells: role of mitochondria-dependent reactive oxygen species.
abstract: 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 AL 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) AL) cells and reactive oxygen species (ROS) inhibitor were used to elucidate the possible mechanism. Our results showed that treatment of AL cells with PFOA for 16 days induced significant mutagenic effects together with the increment of ROS, superoxide anions (O2(.-)), and nitrogen oxide (NO) levels, while treatment of ρ(0) AL cells did not have much change. Concurrent treatment of AL cells with ROS inhibitor significantly decreased the mutagenic potential of PFOA. In addition, caspase activities in AL 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 AL cells, and mitochondria-dependent ROS plays an important role in this process. This provides a direct base for PFOA mediated cancer induction.
authors.affiliation: Key Laboratory of Ion Beam Bioengineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, Anhui, PR China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Zhao
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.forename: Shaopeng
authors.initials: S
authors.lastname: Chen
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhao
authors.forename: Feng
authors.initials: F
authors.lastname: Gu
authors.forename: An
authors.initials: A
authors.lastname: Xu
authors.forename: Lijun
authors.initials: L
authors.lastname: Wu
mesh_terms: D000818:Animals; D002210:Caprylates / Q000633:toxicity*; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D004272:DNA, Mitochondrial / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity; D005466:Fluorocarbons / Q000633:toxicity*; D006801:Humans; D009153:Mutagens / Q000633:toxicity*; D009369:Neoplasms / Q000139:chemically induced; D017382:Reactive Oxygen Species / Q000494:pharmacology; D013481:Superoxides / Q000494:pharmacology
chemical_list: D002210:Caprylates; D004272:DNA, Mitochondrial; D004785:Environmental Pollutants; D005466:Fluorocarbons; D009153:Mutagens; D017382:Reactive Oxygen Species; D013481:Superoxides; C023036:perfluorooctanoic acid; D020169:Caspases