The role of oxidative clustered DNA lesions during breast cell transformation / by Charles-Thomas D. Cooke.

Summary Breast cancer is the most common non-skin cancer and the second leading cause of cancer-related death in women in the United States. There are several environmental and genetic risk factors for the disease, which may induce different types of DNA damage. Carcinogens, such as polycyclic aromatic hydrocarbons (PAHs), may play a role in the initiation of breast cancer. Benzo[a]pyrene (B[a]P) is one of the most widely studied PAHs and it has been shown to induce transformation of normal breast cells, which may be the result of gene alterations. This study hypothesizes that unstable DNA adducts and reactive oxygen species induce multiple lesions that are in close proximity to one another, termed Oxidative Clustered DNA Lesions (OCDLs). Normal early and late passage primary breast tissue-derived cells were treated with B[a]P and the levels of OCDLs and chromosomal aberrations were determined. This study found that: 1) there is an accumulation of various types of complex DNA damage, including OCDLs, in primary breast cells exposed to B[a]P; 2) after exposure to B[a]P, there is an increase in the number of chromosomal aberrations, which have been reported to be directly linked to genetic instability, mutagenesis and cancer; 3) there is a strong positive correlation between the number of OCDLs and the number of chromosomal aberrations. In conclusion, these results provide an indication that OCDLs may play a significant role during transformation of normal primary breast cells.
General notePresented to the faculty of the Department of Biology.
General noteAdvisor: George Sigounas
Dissertation noteM.S. East Carolina University 2007
Bibliography noteIncludes bibliographical references (leaves 82-89).
Genre/formAcademic theses.
Genre/formAcademic theses.
Genre/formThèses et écrits académiques.

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