Proton-induced DNA damage promotes integration of foreign plasmid DNA into human genome.

High-risk human papillomaviruses (HPVs) cause virtually all cervical cancer cases and are also associated with other types of anogenital and oropharyngeal cancers. Normally, HPV exists as a circular episomal DNA in the infected cell. However, in some instances, it integrates into the human genome in such a way as to enable increased expression of viral oncogenes, thereby leading to carcinogenesis. Since viral integration requires breaks in both viral and human genomes, DNA damage likely plays a key role in this critical process. One potentially significant source of DNA damage is exposure to elevated doses of ionizing radiation. Natural background radiation is ubiquitous; however, some populations, including radiological workers, radiotherapy patients, and astronauts, are exposed to significantly higher radiation doses, as well as to different types of radiation such as particle radiation. We hypothesize that ionizing radiation-induced DNA damage facilitates the integration of HPV into the human genome, increasing the risk of developing HPV-related cancers in the exposed population. To test this, we first determined the kinetics of DNA damage in keratinocytes exposed to ionizing radiation (protons) by assessing γ-H2AX foci formation using immunofluorescence (direct damage), and also measured ROS and 8-oxoG levels