Analysis of Complex DNA Damage Associated with Tumor Growth

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Nicholas Foster Ferguson (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Advisor

Alexandros Georgakilas

Abstract: The innate response of a fully functioning immune system's ability to recognize and react to the growth of a tumor by releasing reactive oxygen species (ROS) may lead to chronic inflammation in many cases. This chronic inflammation fueled by a healthy immune system will release enough ROS in unaffected areas that distant tissues begin to show signs of oxidatively induced stress. Focusing on this issue we analyzed tissues proximal and distal to tumor implantation sites of C57BL/6 mice. These mice were sacrificed two weeks into the developmental stages of the subcutaneous syngeneic grafts of either B16 melanoma or NSC-224131 Lewis lung carcinoma. A separate group had sterile phosphate buffer solution injected subcutaneously to serve as the control in this experiment and were sacrificed at the same time as their counterparts in the other two cohorts. This experiment focuses on the double strand breaks (DSB) and oxidatively induced non-DSB clustered lesions (OCDLs) analysis shows evidence of elevated levels of stated damage in tumor bearing mice when compared to age matched control cohort mice. Gel electrophoresis and number average length analysis (NALA) were able to determine the effect of tumor growth on tissues. The kidney was the most affected tissues due to the results that showed elevated susceptibility to ROS in the presence of either tumor. Epidemiological studies have established associations between oxidatively induced stress and the pathogenesis of diseases specifically carcinogenesis in cases of chronic inflammation. Using OCDLs as biomarkers may prove to be essential to establishing a connection between oxidative stress mediating environments and tumor growth. This experiment will specifically focus on two prolific tumors and their initial interaction with a fully functioning immune system when compared to typical inflammatory responses and the ability of a strong antioxidant to reduce the presence of ROS. 

Additional Information

Publication

Thesis

Date: 2012

Keywords

Biology, carcinoma, DNA, lesion, Melanoma, tempol

Subjects

DNA damage

Inflammation

Tumors

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