No difference in the level of gastric mucosal cell apoptosis and proliferation in Helicobacter pylori-colonized p53 heterozygous knockout mice.
BACKGROUND
We previously reported that attenuated epithelial apoptosis and enhanced proliferation in comparison with mice might link to the specific carcinogenesis in Mongolian gerbils and suggested that the difference in both strains might be due to a difference in genetic background. p53 is a well-known tumour suppressor gene, mutation of which is also known to be involved in gastric cancer formation.


OBJECTIVE
The present study was designed to examine the level of gastric epithelial apoptosis and proliferation in p53 heterozygous knockout mice (p53+/-) colonized with Helicobacter pylori (Sydney strain: SS1).


METHODS
Female p53+/- mice and wild-type controls were orally inoculated with SS1 and the stomachs were examined 24 weeks later. DNA fragmentation was measured by levels of cytoplasmic mono- & oligo-nucleosomes as well as by the TUNEL method. Gastric mucosal proliferative activity was morphometrically evaluated from the PCNA-stained tissue specimens. Gastric mucosal myeloperoxidase (MPO) activity was measured to evaluate mucosal inflammation.


RESULTS
DNA fragmentation and the number of TUNEL-positive cells, as well as PCNA-positive cell number increased significantly in both groups of H. pylori-infected mice, suggesting that levels of apoptosis and proliferation may be independent of a deficiency of one p53 allele. MPO activity in p53+/- mice and wild-type controls increased to the same level.


CONCLUSIONS
Although H. pylori inoculation per se induces an increase in cell turnover in mice, heterozygous mutation of p53 did not significantly modify the balance in cell apoptosis and proliferation.
Suzuki
H
H
Department of Internal Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan. hsuzuki@sc.itc.keio.ac.jp
Miyazawa
M
M
Kai
A
A
Suzuki
M
M
Suematsu
M
M
Miura
S
S
Ishii
H
H
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D053938:DNA Fragmentation; D005260:Female; D005753:Gastric Mucosa / Q000201:enzymology / Q000473:pathology*; D016481:Helicobacter Infections / Q000382:microbiology / Q000473:pathology*; D016480:Helicobacter pylori / Q000302:isolation & purification*; D006579:Heterozygote; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D009195:Peroxidase / Q000378:metabolism; D013045:Species Specificity; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D016159:Tumor Suppressor Protein p53; D009195:Peroxidase