Department of Biology

Depleted uranium exposure disrupts mitochondrial ultrastructure and function in zebrafish

Dr. Matthew Salanga
Northern Arizona University

November 9, 2022
4-5pm

Hosted By Dr. Ramji Bhandari

Human exposure to depleted uranium is a public health problem disproportionally affecting underserved communities, such as the Navajo people in the southwestern U.S. and veterans of modern warfare. Legacy uranium mines peppering the Navajo Nation represent unabated contamination sources affecting soil, water, and air. In combat, anti-armor projectiles containing depleted uranium shed shrapnel and uranium oxide microparticles upon impacting a hard target that contaminates the local environment. Research into uranium chemical toxicity has drawn varied interpretations with the mechanisms of toxicity still poorly understood. In our lab, we use zebrafish at varying life stages to study the impact of uranium toxicity associated with different exposure routes and at levels often below the EPA’s Maximum Contaminant Level. Waterborne exposures are useful for modeling inhalation and ingestion and best align with exposure routes common to the Navajo people. On the other hand, we developed a novel microimplantation method to emulate shrapnel wounds, like those in warfare. Preliminary data from zebrafish experiments reveal several concerning outcomes, including decreased levels of cytoplasmic NADH and FADH for waterborne exposures; and disrupted mitochondrial ultrastructure in our shrapnel model. Additionally, proximity-dependent toxicity was observed as disrupted mitochondria near the uranium implant sites and not on the contralateral side of the animal or among sham subjects. To explain the observed mitochondrial disruption, we are testing the hypothesis that uranium causes mitochondrial genome damage by adducting DNA’s phosphate backbone leading to DNA damage and diminished mitochondrial function. We are testing our hypothesis using two highly sensitive methods for quantifying DNA lesions: long-run real-time PCR (LORDQ) and semi-long run (SLR) real-time PCR. Thus far, preliminary data suggest an increase in lesion frequency for exposed zebrafish, supporting our hypothesis.