Cancer-associated strains of Helicobacter pylori stimulate DNA synthesis in IEC-6 cells.
OBJECTIVE
To determine whether water extracts of Helicobacter pylori strains, which express CagA, can influence DNA synthesis in untransformed intestinal epithelial cells in vitro.


METHODS
We used water extracts produced from H. pylori strains (A, B, C), collected from gastric mucosa of gastric cancer patients. Strain A was CagA+/VacA+ whereas strains B and C were CagA+/VacA-. Water extracts from Helicobacter mustelae and Escherichia coli were used as controls.


METHODS
IEC-6 cells (small intestinal epithelial cell line from germ-free rats) were incubated with various concentrations of the bacterial extracts for 24 h. The cells were labelled with [3H]methylthymidine for 4 h and thereafter processed for autoradiography. DNA synthesis was evaluated by the labelling index (LI%).


RESULTS
Water extracts from CagA-positive strains of H. pylori, with or without the capacity to produce vacuolating toxins, increased the LI in a dose-related manner (P < 0.05). The water extracts of E. coli significantly increased the LI (P < 0.001), whereas the water extracts of H. mustelae did not affect DNA synthesis.


CONCLUSIONS
Cancer-associated, CagA-positive strains of H. pylori stimulate DNA synthesis in epithelial cells in vitro, independently of their ability to produce VacA toxin. Our findings suggest that unknown mitogenic components of H. pylori may contribute to the increased cell proliferation observed in the histological stages preceding gastric cancer.
Bark
J
J
Department of Medicine, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
Enroth
H
H
Engstrand
L
L
Uribe
A
A
D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism; D016998:Helicobacter / Q000378:metabolism; D016480:Helicobacter pylori / Q000378:metabolism*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013274:Stomach Neoplasms / Q000382:microbiology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori; D004247:DNA