Abstract

High-risk human papillomavirus (HPV) is the causative agent of cervical cancer. Integration of the HPV genome into the host genome is a key event in cervical carcinogenesis, with oxidative stress (OS) likely playing a major role in promoting DNA damage, and subsequently, integration. In our current study, we demonstrated a chain of events leading from the induction of OS, to DNA damage, and then to viral integration. Induction of OS by either virus-mediated factors, such as expression of E6*, a splice variant of the E6 oncogene, or by exogenous factors led to DNA damage in normal oral keratinocytes and in cervical keratinocytes containing episomal HPV16. We found that OS increased the integration rate for both foreign DNA and HPV, while antioxidants reduced the integration frequency. We also demonstrated a significant variability in ROS levels in patient-derived cervical specimens, which may reflect differences in susceptibility to cervical cancer between women.

LLU Discipline

Biochemistry

Department

Basic Sciences

School

School of Medicine

First Advisor

Duerksen-Hughes, Penelope J.

Second Advisor

Casiano, Carlos A.

Third Advisor

Wang, Charles

Fourth Advisor

Unternaehrer, Julia

Fifth Advisor

Siddighi, Sam

Sixth Advisor

Filippov, Valery

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

2016

Date (Title Page)

6-2016

Language

English

Library of Congress/MESH Subject Headings

Uterine Cervical Neoplasms; Oncogenic Viruses; Papillomavirus; Human; Carcinoma; Squamous Cell; Oncogene Proteins; Viral

Subject - Local

Human Papillomavirus; Cervical cancer; Carcinogenesis; Viral integration; Virus-mediated factors; Cancer susceptibility

Type

Dissertation

Page Count

155

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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