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Archived Comments for: A new approach to design safe CNTs with an understanding of redox potential

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  1. In support of a better understanding of redox potential in toxicology

    James Samet, National Health and Environmental Effects Research Laboratory

    7 September 2015

    Dear Dr. Cassee

    I read with great interest the excellent commentary that you co-authored with Drs. Tsuruoka and Castranova in the September 2, 2013 issue of Particle and Fibre Toxicology.

    While there is ample evidence to support the notion that redox potential is a fundamental determinant of the toxicity of many xenobiotics, the significance of redox reactions has not gained proper attention in toxicology.

    One impediment has been a lack of specificity in the terminology used in the field, with ¿oxidant stress¿, ¿free radical reactions¿, ¿oxidant/antioxidant imbalance¿, ¿ROS¿, etc. used informally (sometimes interchangeably) to refer to events involving redox reactions that ultimately cause a change in the ratio of reduced/ oxidized glutathione (EGSH) and other redox pairs within the cell.

    Methodological limitations have also hampered appreciation of the relevance of redox reactions in toxicology. Regrettably, a focus on analytical approaches aimed at identifying oxidative damage to lipids, proteins and nucleic acids with ever increasing sensitivity has provided few insights into the mechanisms through which xenobiotic exposures disrupt redox homeostasis in the cell. Such perturbations lead to a loss of signaling quiescence by promoting the oxidation of regulatory protein thiols, thereby initiating cellular responses that range from adaptive gene expression to cell death.

    In recent years, a new generation of fluorogenic small molecule and genetically-encoded sensors has been introduced to the field of redox biology. These sensors are capable of reporting in real time on the concentration of specific reactive oxygen species or EGSH with unprecedented sensitivity and can be targeted to specific subcellular compartments. Our laboratory and others have been using these sensors in various toxicological applications (1-3). The field will surely gain as these new sensors find broader utilization in laboratories conducting toxicological research.

    Similarly, research and risk assessment endeavors alike will be well served by the recognition of redox potential as a physicochemical determinant of the toxicity of xenobiotic materials, and of intracellular redox homeostasis as critical target in toxicology.



    James M. Samet, PhD, MPH, DABT
    Clinical Research Branch
    Environmental Public Health Division
    National Health and Environmental Effects Research Laboratory
    U.S. Environmental Protection Agency
    Samet.James@EPA.gov


    1.Cheng WY, Currier J, Bromberg PA, Silbajoris R, Simmons SO, Samet JM: Linking oxidative events to inflammatory and adaptive gene expression induced by exposure to an organic particulate matter component. Environmental health perspectives 2012, 120:267-274.

    2.Cheng WY, Tong H, Miller EW, Chang CJ, Remington J, Zucker RM, Bromberg PA, Samet JM, Hofer TP: An integrated imaging approach to the study of oxidative stress generation by mitochondrial dysfunction in living cells. Environmental health perspectives 2010, 118:902-908.

    3.Gibbs-Flournoy EA, Simmons SO, Bromberg PA, Dick TP, Samet JM: Monitoring intracellular redox changes in ozone-exposed airway epithelial cells. Environmental health perspectives 2013, 121:312-317.

    Competing interests

    No competing interests to declare

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