Silver impairs neurodevelopment: studies in PC12 cells.
BACKGROUND
Exposure to silver is increasing because of silver nanoparticles in consumer products.


OBJECTIVE
Many biological effects of silver entail actions of Ag+ (monovalent silver ions), so we used neuronotypic PC12 cells to evaluate the potential for silver to act as a developmental neurotoxicant, using chlorpyrifos (CPF), a pesticide known to evoke developmental neurotoxicity, as a positive control for comparison.


RESULTS
In undifferentiated cells, a 1-hr exposure to 10 microM Ag+ inhibited DNA synthesis more potently than did 50 microM CPF; it also impaired protein synthesis but to a lesser extent than its effect on DNA synthesis, indicating a preferential effect on cell replication. Longer exposures led to oxidative stress, loss of viability, and reduced numbers of cells. With the onset of cell differentiation, exposure to 10 microM Ag+ evoked even greater inhibition of DNA synthesis and more oxidative stress, selectively impaired neurite formation without suppressing overall cell growth, and preferentially suppressed development into the acetylcholine phenotype in favor of the dopamine phenotype. Lowering the exposure to 1 microM Ag+ reduced the net effect on undifferentiated cells. However, in differentiating cells, the lower concentration produced an entirely different pattern, enhancing cell numbers by suppressing ongoing cell death and impairing differentiation in parallel for both neurotransmitter phenotypes.


CONCLUSIONS
Our results show that silver has the potential to evoke developmental neurotoxicity even more potently than known neurotoxicants, such as CPF, and that the spectrum of effects is likely to be substantially different at lower exposures that do not show signs of outright toxicity.
Powers
Christina M
CM
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Wrench
Nicola
N
Ryde
Ian T
IT
Smith
Amanda M
AM
Seidler
Frederic J
FJ
Slotkin
Theodore A
TA
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004390:Chlorpyrifos / Q000633:toxicity; D004247:DNA / Q000096:biosynthesis; D004298:Dopamine / Q000378:metabolism; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D010575:Pesticides / Q000633:toxicity; D051381:Rats; D012834:Silver / Q000008:administration & dosage / Q000633:toxicity*
D010575:Pesticides; D012834:Silver; D004247:DNA; D004390:Chlorpyrifos; D000109:Acetylcholine; D004298:Dopamine