The antioxidant N-acetylcysteine protects from lung emphysema but induces lung adenocarcinoma in mice

被引:35
作者
Breau, Marielle [1 ,2 ]
Houssaini, Amal [1 ,2 ]
Lipskaia, Larissa [1 ,2 ]
Abid, Shariq [1 ,2 ]
Born, Emmanuelle [1 ,2 ]
Marcos, Elisabeth [1 ,2 ]
Czibik, Gabor [1 ,2 ]
Attwe, Aya [1 ,2 ]
Beaulieu, Delphine [1 ,2 ]
Palazzo, Alberta [3 ]
Flaman, Jean-Michel [3 ]
Bourachot, Brigitte [4 ]
Collin, Guillaume [3 ]
Jeanne Tran Van Nhieu [5 ]
Bernard, David [3 ]
Mechta-Grigoriou, Fatima [4 ]
Adnot, Serge [1 ,2 ]
机构
[1] Hop Henri Mondor, AP HP, INSERM U955, Dept Physiol Explorat Fonct, Creteil, France
[2] Hop Henri Mondor, AP HP, DHU A TVB, Creteil, France
[3] Univ Lyon, UMR INSERM U1052, Ctr Rech Cancerol Lyon, CNRS 5286, Lyon, France
[4] Inst Curie, INSERM U830, Equipe Labelisee LNCC, Stress & Canc Lab, Paris, France
[5] Hop Henri Mondor, AP HP, Dept Pathol, Creteil, France
关键词
OXIDATIVE STRESS; CELL SENESCENCE; COPD; EXACERBATIONS; ANGIOGENESIS; PREVENTION; MORTALITY; TRIALS;
D O I
10.1172/jci.insight.127647
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Oxidative stress is a major contributor to chronic lung diseases. Antioxidants such as N-acetylcysteine (NAC) are broadly viewed as protective molecules that prevent the mutagenic effects of reactive oxygen species. Antioxidants may, however, increase the risk of some forms of cancer and accelerate lung cancer progression in murine models. Here, we investigated chronic NAC treatment in aging mice displaying lung oxidative stress and cell senescence due to inactivation of the transcription factor JunD. which is downregulated in diseased human lungs. NAC treatment decreased lung oxidative damage and cell senescence and protected from lung emphysema but concomitantly induced the development of lung adenocarcinoma in 50% of JunD-deficient mice and 10% of aged control mice. This finding constitutes the first evidence to our knowledge of a carcinogenic effect of antioxidant therapy in the lungs of aged mice with chronic lung oxidative stress and warrants the utmost caution when considering the therapeutic use of antioxidants.
引用
收藏
页数:11
相关论文
共 23 条
[21]   Endoplasmic reticulum calcium release through ITPR2 channels leads to mitochondrial calcium accumulation and senescence [J].
Wiel, Clotilde ;
Lallet-Daher, Helene ;
Gitenay, Delphine ;
Gras, Baptiste ;
Le Calve, Benjamin ;
Augert, Arnaud ;
Ferrand, Mylene ;
Prevarskaya, Natalia ;
Simonnet, Helene ;
Vindrieux, David ;
Bernard, David .
NATURE COMMUNICATIONS, 2014, 5
[22]   Antioxidants and prevention of chronic disease [J].
Willcox, JK ;
Ash, SL ;
Catignani, GL .
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION, 2004, 44 (04) :275-295
[23]   Link between COPD and lung cancer [J].
Young, Robert P. ;
Hopkins, Raewyn J. .
RESPIRATORY MEDICINE, 2010, 104 (05) :758-759