High salt diets dose-dependently promote gastric chemical carcinogenesis in Helicobacter pylori-infected Mongolian gerbils associated with a shift in mucin production from glandular to surface mucous cells.
Intake of salt and salty food is known as a risk factor for gastric carcinogenesis. To examine the dose-dependence and the mechanisms underlying enhancing effects, Mongolian gerbils were treated with N-methyl-N-nitrosourea (MNU), Helicobacter pylori and food containing various concentrations of salt, and were sacrificed after 50 weeks. Among gerbils treated with MNU and H. pylori, the incidences of glandular stomach cancers were 15% in the normal diet group and 33%, 36% and 63% in the 2.5%, 5% and 10% NaCl diet groups, showing dose-dependent increase (p < 0.01). Intermittent intragastric injection of saturated NaCl solution, in contrast, did not promote gastric carcinogenesis. In gerbils infected with H. pylori, a high salt diet was associated with elevation of anti-H. pylori antibody titers, serum gastrin levels and inflammatory cell infiltration in a dose-dependent fashion. Ten percent NaCl diet upregulated the amount of surface mucous cell mucin (p < 0.05), suitable for H. pylori colonization, despite no increment of MUC5AC mRNA, while H. pylori infection itself had an opposing effect, stimulating transcription of MUC6 and increasing the amount of gland mucous cell mucin (GMCM). High salt diet, in turn, decreased the amount of GMCM, which acts against H. pylori infection. In conclusion, the present study demonstrated dose-dependent enhancing effects of salt in gastric chemical carcinogenesis in H. pylori-infected Mongolian gerbils associated with alteration of the mucous microenvironment. Reduction of salt intake could thus be one of the most important chemopreventive methods for human gastric carcinogenesis.
Kato
Sosuke
S
Division of Oncological Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Tsukamoto
Tetsuya
T
Mizoshita
Tsutomu
T
Tanaka
Harunari
H
Kumagai
Toshiko
T
Ota
Hiroyoshi
H
Katsuyama
Tsutomu
T
Asaka
Masahiro
M
Tatematsu
Masae
M
D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D000595:Amino Acid Sequence; D000821:Animal Feed; D000818:Animals; D001483:Base Sequence; D001835:Body Weight / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori / Q000502:physiology*; D008297:Male; D008770:Methylnitrosourea / Q000494:pharmacology; D008969:Molecular Sequence Data; D008986:Mongolia; D009077:Mucins / Q000096:biosynthesis* / Q000235:genetics; D016415:Sequence Alignment; D012965:Sodium Chloride / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology*
D009077:Mucins; D012965:Sodium Chloride; D008770:Methylnitrosourea