Mechanism of Silver Nanoparticles Action on Insect Pigmentation Reveals Intervention of Copper Homeostasis. Atanu Duttaroy¹, Najealicka Armstrong¹, Malaisamy Ramamoorthy², Delina Lyon², Kimberly Jones². 1) Dept Biol, Howard Univ, Washington, DC; 2) Department of Civil and Environmental Engineering, Howard University, Washington, DC.

   Silver nanoparticles (AgNPs), like almost all nanoparticles, are potentially toxic beyond certain concentration because past that concentration survival of the organism is compromised due to scores of pathophysiological abnormalities. But the mechanism of AgNP toxicity remains undetermined. Instead of applying a toxic dose, we attempted to monitor the effects of AgNPs at a nonlethal concentration on wild type Drosophila melanogaster by exposing them throughout their development. All adult flies raised in AgNP doped food shows that up to 50 ppm (125 g/gm of food) concentration AgNP has no negative influence on median survival however, these flies appeared uniformly lighter in body color due to the loss of melanin pigments from their cuticle. Additionally, fertility and vertical movement ability were compromised due to AgNP feeding. Determination of the amount of free Ag+ led us to claim that the observed biological effects have resulted from the AgNPs and not from free Ag. Biochemical analysis suggests that the activity of copper dependent enzymes, namely tyrosinase and Cu-Zn superoxide dismutase are decreased significantly following the consumption of AgNPs, despite the constant level of copper present in the tissue. Consequently, we propose a mechanism whereby consumption of excess AgNPs in association with membrane bound copper transporter proteins cause sequestration of copper, thus creating a condition that resembles copper starvation. This model also explains the cuticular demelanization effect resulting from AgNP since tyrosinase activity is essential for melanin biosynthesis. Finally, we claim that Drosophila, an established genetic model system, can be well utilized for further understanding of the biological effects of nanoparticles.