Effects of silver nanoparticles on oxidative DNA damage-repair as a function of p38 MAPK status: A comparative approach using human Jurkat T cells and the nematode Caenorhabditis elegans

• Published in: Environmental and molecular mutagenesis 2014-03, Vol.55 (2), p.122-133
• Main Authors: Chatterjee, Nivedita, Eom, Hyun Jeong, Choi, Jinhee
• Format: Article
• Language: English
• Subjects: 8-oxo-GTPases; 8OHdG; Animals; Anti-Infective Agents - toxicity; Caenorhabditis elegans; Caenorhabditis elegans - enzymology; Caenorhabditis elegans Proteins - metabolism; Caenorhabditis elegans Proteins - physiology; Cell Survival; Deoxyribonuclease (Pyrimidine Dimer) - genetics; Deoxyribonuclease (Pyrimidine Dimer) - metabolism; DNA Damage; DNA glycosylases; DNA Glycosylases - metabolism; DNA Repair; DNA Repair Enzymes - metabolism; Gene Expression; Humans; Jurkat Cells; Metal Nanoparticles - toxicity; Mitogen-Activated Protein Kinases - physiology; Nematoda; Oxidation-Reduction; Oxidative Stress - genetics; p38 MAPK; p38 Mitogen-Activated Protein Kinases - physiology; Phosphoric Monoester Hydrolases - metabolism; PMK-1; Silver - toxicity; silver nanoparticles
• ISSN: 0893-6692; 1098-2280
• DOI: 10.1002/em.21844

The large‐scale use of silver nanoparticles (AgNPs) has raised concerns over potential impacts on the environment and human health. We previously reported that AgNP exposure causes an increase in reactive oxygen species, DNA damage, and induction of p38 MAPK and PMK‐1 in Jurkat T cells and in Caenorhabditis elegans. To elucidate the underlying mechanisms of AgNP toxicity, here we evaluate the effects of AgNPs on oxidative DNA damage–repair (in human and C. elegans DNA glycosylases hOGG1, hNTH1, NTH‐1, and 8‐oxo‐GTPases—hMTH1, NDX‐4) and explore the role of p38 MAPK and PMK‐1 in this process. Our comparative approach examined viability, gene expression, and enzyme activities in wild type (WT) and p38 MAPK knock‐down (KD) Jurkat T cells (in vitro) and in WT and pmk‐1 loss‐of‐function mutant strains of C. elegans (in vivo). The results suggest that p38 MAPK/PMK‐1 plays protective role against AgNP‐mediated toxicity, reduced viability and greater accumulation of 8OHdG was observed in AgNP‐treated KD cells, and in pmk‐1 mutant worms compared with their WT counterparts, respectively. Furthermore, dose‐dependent alterations in hOGG1, hMTH1, and NDX‐4 expression and enzyme activity, and survival in ndx‐4 mutant worms occurred following AgNP exposure. Interestingly, the absence or depletion of p38 MAPK/PMK‐1 caused impaired and additive effects in AgNP‐induced ndx‐4(ok1003); pmk‐1(RNAi) mutant survival, and hOGG1 and NDX‐4 expression and enzyme activity, which may lead to higher accumulation of 8OHdG. Together, the results indicate that p38 MAPK/PMK‐1 plays an important protective role in AgNP‐induced oxidative DNA damage–repair which is conserved from C. elegans to humans. Environ. Mol. Mutagen. 55:122–133, 2014. © 2013 Wiley Periodicals, Inc.