TY - JOUR

T1 - The role of intracellular redox imbalance in nanomaterial induced cellular damage and genotoxicity

T2 - a review

AU - Kermanizadeh, Ali

AU - Chauché, Caroline

AU - Brown, David M

AU - Loft, Steffen

AU - Møller, Peter

N1 - © 2014 Wiley Periodicals, Inc.

PY - 2015/3

Y1 - 2015/3

N2 - The terms oxidative stress, free radical generation, and intracellular antioxidant protection have become part of everyday nanotoxicology terminology. In recent years, an ever increasing number of in vitro and in vivo studies have implicated disruptions to the redox balance and oxidative stress as one of the main contributors to nanomaterial (NM) induced adverse effects. One of the most important and widely investigated of these effects is genotoxicity. In general, systems that defend an organism against oxidative damage to DNA are very complex and include prevention of reactive oxygen species (ROS) production, neutralizing ROS (scavengers), enzymatic nucleotide pool sanitation, and DNA repair. This review discusses the importance of the maintenance of the redox balance in this context before examining studies that have investigated engineered NM induced redox imbalance and genotoxicity. Furthermore, we identify data gaps, and highlight a number of issues that exist with the methodologies that are routinely utilized to investigate intracellular ROS production or anti-oxidant depletion. We conclude that for a large number of engineered NM types changes in the redox balance toward oxidative stress are normally associated with DNA damage.

AB - The terms oxidative stress, free radical generation, and intracellular antioxidant protection have become part of everyday nanotoxicology terminology. In recent years, an ever increasing number of in vitro and in vivo studies have implicated disruptions to the redox balance and oxidative stress as one of the main contributors to nanomaterial (NM) induced adverse effects. One of the most important and widely investigated of these effects is genotoxicity. In general, systems that defend an organism against oxidative damage to DNA are very complex and include prevention of reactive oxygen species (ROS) production, neutralizing ROS (scavengers), enzymatic nucleotide pool sanitation, and DNA repair. This review discusses the importance of the maintenance of the redox balance in this context before examining studies that have investigated engineered NM induced redox imbalance and genotoxicity. Furthermore, we identify data gaps, and highlight a number of issues that exist with the methodologies that are routinely utilized to investigate intracellular ROS production or anti-oxidant depletion. We conclude that for a large number of engineered NM types changes in the redox balance toward oxidative stress are normally associated with DNA damage.

KW - Antioxidants/pharmacology

KW - DNA Damage/drug effects

KW - DNA Repair/drug effects

KW - Free Radicals/chemistry

KW - Humans

KW - Nanostructures/toxicity

KW - Oxidative Stress

KW - Reactive Oxygen Species/metabolism

KW - Signal Transduction/drug effects

U2 - 10.1002/em.21926

DO - 10.1002/em.21926

M3 - Review article

C2 - 25427446

VL - 56

SP - 111

EP - 124

JO - Environmental and molecular mutagenesis

JF - Environmental and molecular mutagenesis

SN - 0893-6692

IS - 2

ER -