Biomedical Sciences ETDs

Publication Date



Mitochondrial DNA (mtDNA) normally occurs in multicellular animals as a double-stranded covalently closed circular form with a contour length of approximately 5 µ. In addition to the normal monomer length circular molecules of 5 µ, circular forms of mtDNA with twice or several times the length of the monomeric form have been described in several systems. Dimers may be found in two forms: 1) unicircular dimers consisting of two monomeric length molecules linked in a head to tail structure, 2) catenated forms with two or more monomers interlocked as links in a chain. The latter are most commonly observed and occur at a frequency of 2-9% in all normal animal cells. The circular dimers, on the other hand, have been described only in a limited number of systems. The specific aims of the research reported here were to study the occurrence of these complex topological forms of mtDNA from leukemic and non-leukemic AKR mice as well as from C57B1/6J mice. The AKR mouse system was chosen as an ideally suited animal model to study these forms of mtDNA in a leukemic system. The AKR mice are an inbred strain in which better than 90% of the population develop spontaneous leukemia between seven and nine months of age. Two AKR control groups were used: The old AKR mice (12-16 months) presumed to be the 10% resistant to leukemia and the young AKR mice (12 weeks) before they develop leukemia. A third control was the C57B1/6J mouse strain; chosen because of its proven low incidence of spontaneous leukemia. The circular dimer form of mtDNA was found at significant levels in the young AKRs and the leukemic AKRs but not in the non-leukemic animals. There was a positive correlation between evidence of circular dimers and progression of the disease state-leukemic mice having the greatest evidence of circular dimers. The finding of circular dimers in preleukemic mice suggests that the occurrence of early subcellular changes is an important cellular modification in the leukemogenic process. It will be of great importance to determine the diagnostic significance of the occurrence of circular dimers and AKR leukemogenesis.

Document Type




Degree Name

Biomedical Sciences

Level of Degree


Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Joseph Victor Scaletti

Second Committee Member

Robert Edwin Anderson

Third Committee Member

Leroy Clarence McLaren