Role of Helicobacter pylori CagA+ infection in determining oxidative DNA damage in gastric mucosa.
BACKGROUND
Although Helicobacter pylori is a risk factor for gastric cancer, the role of the bacterium in the development of this malignancy is not defined precisely. Reactive oxygen species (ROS) could play an important role in carcinogenesis by inducing DNA damage. The aims of the present study were: 1) to assess the production of ROS and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA injury, in gastric mucosa, according to H. pylori status and cytotoxic associated gene product A (CagA); 2) to determine the relationship between ROS generation and amount of 8-OHdG.


METHODS
Gastric biopsy specimens were obtained from 60 consecutive patients. ROS generation was measured by luminol enhanced chemiluminescence. 8-OHdG detection was performed by an immunoperoxidase method, using a specific anti 8-OHdG monoclonal antibody.


RESULTS
40/60 patients (67%) were H. pylori-positive. ROS generation was significantly higher in patients positive for H. pylori infection as compared to negative. 8-OHdG detection was performed in 30 patients in which CagA presence was also investigated. High expression of 8-OHdG was detected in 14/20 (70%) H. pylori-positive patients (13 CagA+ and 1 CagA-) and in 2/10 (20%) H. pylori-negative patients. A significant correlation was found between ROS production and 8-OHdG content.


CONCLUSIONS
H. pylori infection by a CagA+ strain is associated with the highest production of ROS to which a severe oxidative DNA damage corresponds. This sequence of events could support the hypothesis that the oxygen-free radicals-mediated damage due to H. pylori cytotoxic strains could be a driving force that leads from chronic gastritis to gastric carcinoma.
Papa
A
A
Institute of Internal Medicine, Giovanni XXIII Cancer Research Center and Institute of General Pathology, Institute of Pathology, Catholic University of Rome, Italy. alfredopapa@hotmail.com
Danese
S
S
Sgambato
A
A
Ardito
R
R
Zannoni
G
G
Rinelli
A
A
Vecchio
F M
FM
Gentiloni-Silveri
N
N
Cittadini
A
A
Gasbarrini
G
G
Gasbarrini
A
A
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D002908:Chronic Disease; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000821:virology; D005756:Gastritis / Q000150:complications / Q000821:virology; D016481:Helicobacter Infections / Q000150:complications / Q000378:metabolism* / Q000821:virology; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000378:metabolism; D013274:Stomach Neoplasms / Q000821:virology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D017382:Reactive Oxygen Species; C080866:cagA protein, Helicobacter pylori; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine