title: Elevated mitochondrial DNA copy number and POL-γ expression but decreased expression of TFAM in murine intestine following therapeutic dose irradiation.
abstract: Mitochondria play pivotal roles in cellular handling of oxygen and in apoptosis, the ordered suicide response of cells to irradiation. The involvement of expression products from the 16.5 kb human mitochondrial genome in these activities has been studied widely. However, little is known about effects of irradiation on mammalian mitochondrial DNA (mtDNA). The relative lack of mtDNA repair mechanisms compared with nuclear DNA (nDNA) predicts particular vulnerability to irradiation. Using a technique developed to ascertain mtDNA:nDNA ratios, we previously showed that this ratio increases dramatically in murine small bowel within 48 hours following whole body irradiation. We now report that those levels continue to rise for four days and remain elevated at close to that level beyond 30 days after 5 Gy of irradiation.We further demonstrate that levels of the mtDNA-specific DNA polymerase-γ (Pol-γ ) also show a sharp and sustained increase during this time course after a 2-Gy dose. Paradoxically, transcription factor A (TFAM), exhibited the directly opposite response.
authors: Department of Radiation Oncology, University of Florida, 2033 Mowry Road, 103633, Gainesville, FL 32610, USA.
authors: Hengshan
authors: H
authors: Zhang
authors: David J
authors: DJ
authors: Maguire
authors: Mei
authors: M
authors: Zhang
authors: Lurong
authors: L
authors: Zhang
authors: Paul
authors: P
authors: Okunieff
mesh_terms: D000818:Animals; D002588:Cesium Radioisotopes; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D018628:Gene Dosage / Q000528:radiation effects*; D006609:High Mobility Group Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012337:RNA, Ribosomal, 18S / Q000235:genetics* / Q000378:metabolism; D014916:Whole-Body Irradiation
chemical_list: D002588:Cesium Radioisotopes; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D012337:RNA, Ribosomal, 18S; C081930:Tfam protein, mouse; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase