Chromosomal alterations in mini organ cultures of human oropharyngeal mucosa cells caused by hydrogen peroxide

Abstract

Background: Oxidative stress is a known exogenous risk factor for carcinogenesis in the head and neck. In addition to exogenous risk factors, the development of head and neck cancer is based on genetic alterations and individual mutagen sensitivity. DNA damage caused by reactive oxygen species (ROS) is not uniformly distributed over the DNA, as certain chromosomes and genes are more likely to be damaged than others. The ability to repair damaged DNA sufficiently is a necessity in order to prevent carcinogenesis. The DNA-damaging effect of ROS, the specific sites of chromosomal changes and DNA repair in those regions require further investigation.

Materials and methods: In order to evaluate DNA damage in macroscopically healthy mucosal tissue of 37 patients with (15) and without cancer (22) of the oropharynx, four different chromosomes (chromosomes 3, 5, 8 and 11) involved in carcinogenesis of the oropharynx were examined. After incubation with H(2)O(2), comet FISH was applied to assess DNA damage of these chromosomes. The extent of DNA repair was evaluated in the same samples after a 24-hour repair period.

Results: H(2)O(2) caused significant DNA damage in oropharyngeal mucosal cells of patients with and without carcinoma. DNA fragmentation of all chromosomes investigated in the two groups was comparable. No differences were observed between mutagen sensitivity of patients suffering from cancer of the oropharynx and those without malignancy for any of the observed chromosomes. On the other hand, chromosomal DNA damage of these specific chromosomes was significantly higher than the average DNA fragmentation of the entire DNA in both groups. DNA repair led to a significant decrease in DNA damage in all groups. Controls tend to have a better DNA repair in all of the analysed chromosomes. However, these differences were not significant.

Conclusion: The increased chromosomal DNA fragmentation in comparison to that of the entire DNA indicates the contribution of the investigated chromosomes to carcinogenesis in the oropharynx. DNA repair in those chromosomes might play a role in carcinogenesis of the oropharynx, but further investigations are warranted.