A comparison of DNA damage signaling in human epithelial cells treated with UVB and 9,10 phenanthrenequinone
Description
TitleA comparison of DNA damage signaling in human epithelial cells treated with UVB and 9,10 phenanthrenequinone
Date Created2023
Other Date2023-05 (degree)
Extent123 pages : illustrations
DescriptionHumans are chronically exposed to environmental risks, including air pollutants and solar UV radiation, which seriously affect human health. 9,10-Phenanthrenequinone (9,10-PQ), a redox-active component found in diesel exhaust particles (DEP), plays a key role in the adverse health effects triggered by air pollution. The first part of my thesis research is to investigate the role of 9,10-PQ in oxidative and mitochondrial stress in human lung epithelial cell lines. The toxicity of 9,10-PQ has been associated with the generation of reactive oxygen species (ROS) via the process of redox cycling, as evidenced by decrease in cell viability and increase in ROS production in A549 and Calu-1 human lung epithelial cells. In addition, 9,10-PQ induced mitochondrial dysfunction in the cells. N-acetylcysteine (NAC) was found to decrease 9,10-PQ toxicity by suppression of intracellular ROS production and partially by inhibition of mitochondrial dysfunction. In the second part of my thesis research, I have uncovered an unexpected role of 9,10-PQ to induce DNA damage responses (DDR) in human lung epithelial cells. We found that 9,10-PQ caused a time- and concentration-dependent activation of DDR proteins in A549 cells and Calu-1 cells. Treatment of the cells with 9,10-PQ caused a suppression of cell proliferation by inhibiting DNA synthesis, and induction of 8-oxo-2'-deoxyguanosine (8-oxo-dG), an oxidative DNA damage indicator, suggesting that 9,10-PQ generated ROS mediated DNA damage.
The last part focused on the effects of UVB on DDR in human keratinocytes. We found that UVB caused dose- and time-dependent activation of DDR in human keratinocytes. DDR signaling in HaCaT cells predominated in S phase cells, when compared to cells in G0/G1 and G2/M. Increases in UVB-induced ROS were noted when HaCaT cells were depleted of glutathione using buthionine sulfoximine (BSO), this had no effect on the UVB-induced DDR. These data demonstrate that UVB induces cell cycle-dependent DNA damage in human keratinocytes, which is independent of oxidative stress.
Taken together, these data provide evidence to compare DNA damage signaling activated by UVB and 9,10-PQ respectively in human epithelial cells.
NotePh.D.
NoteIncludes bibliographical references
Genretheses
LanguageEnglish
CollectionSchool of Graduate Studies Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
Statistical Profile