Radiation Effects on Levels of Total Mitochondrial DNA and DNA Bearing the Common Deletion in a Pearson's Syndrome Pedigree

Abstract

Mutations in mitochondrial DNA (mtDNA) correlate with aging and oxidative stress and they appear in a host of degenerative diseases. Little is known about how ionizing radiation might contribute to the appearance of these mutations, however. Here we quantify a specific deletion of 4977 base pairs (known as the “common deletion”) as a function of X‐ray dose using real‐time PCR. We grew lymphoblast cells derived from a patient with Pearson's Marrow/Pancreas syndrome (known to contain elevated levels of the common deletion) as well as normal cells derived from the patient's mother and sister. We irradiated the cells with doses of 0.5–5 Gy of gamma radiation. Total (nuclear and mitochondrial) and mitochondrial DNA extracts were then analyzed along with cloned plasmids that served as quantification controls. The deletion was only measurable in the Pearson's Syndrome cells and results showed elevated levels with radiation dose. The total mtDNA remained relatively constant in these cells. In contrast, the levels of total mtDNA increased in the normal control cells derived from the patient's mother and sister.This research is supported by a Henry Dreyfus Teacher‐Scholar Award.