Demonstrating or verifying a current or past exposure to an environmental mitochondrial toxin or toxicant is extraordinarily difficult. Thus, there is a pressing need to develop a biomarker for exposure to environmental mitochondrial inhibitors. @entity3788 , an environmental toxicant, is a potent inhibitor of the mitochondrial electron transfer chain. @entity3788 specifically inhibits complex I throughout the body and brain, thereby producing systemic @entity2383 . As such, @entity3788 is a prototypical clinically relevant, environmental mitochondrial toxicant that may be used as an ideal initial platform to develop accessible biomarkers of exposure. The over-arching goal of this work is to explore and validate peripheral (blood and skeletal muscle) DNA damage as a biomarker of mitochondrial toxicant exposure using the @entity35 @entity3788 model. In this effort, we utilized an extremely sensitive quantitative polymerase chain reaction (QPCR)-based assay that simultaneously allows the assessment of multiple forms of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) damage. We found mtDNA damage in blood is detected after subclinical @entity3788 exposure and the damage persists even after complex I activity has returned to normal. With a more sustained @entity3788 exposure, mtDNA damage is also detected in skeletal muscle, suggesting that mtDNA damage in this tissue simply lags behind blood. Using the QPCR-based assay, we have no evidence for nDNA damage in peripheral tissues after @entity3788 exposure either acutely or chronically. Overall, these data support the idea that mtDNA damage in peripheral tissues in the @entity3788 model may provide a biomarker of past or ongoing mitochondrial toxin exposure.

Mitochondrial DNA damage as a peripheral biomarker for mitochondrial toxin exposure in XXXX .

@entity35 :: ('10116', 'Species') :: ['rat'] @entity3788 :: ('MESH:D012402', 'Chemical') :: ['Rotenone', 'rotenone'] @entity2383 :: ('MESH:D028361', 'Disease') :: ['mitochondrial impairment']
@entity35 :: (10116,Species) :: ['rats']
