Enhancement by interleukin-1 beta of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats: a possible mechanism for Helicobacter pylori-associated gastric carcinogenesis.
The effect of prolonged administration of the cytokine interleukin (IL)-1beta on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was examined in Wistar rats. In addition, we examined the effects on the proliferating cell nuclear antigen (PCNA) labeling index and the hepatocyte growth factor (HGF) immunoreactivity of the gastric mucosa. The rats received intraperitoneal injections of 0.1 or 0.3 microg/kg body weight of IL-1beta every other day after oral treatment with MNNG for 25 weeks. Long-term administration of IL-1beta at high dose, but not at low dose, significantly increased the incidence of gastric cancer in week 52. Administration of IL-1beta at high dose also significantly increased the labeling index and the HGF immunoreactivity of the gastric antral mucosa, and induced inflammatory cell infiltration and glandular atrophy of the gastric mucosa. Because IL-1beta production in the gastric mucosa is increased in patients with Helicobacter pylori-associated gastritis and eradiation of the organism significantly decreases the IL-1beta production, these findings suggest that Helicobacter pylori-associated gastric carcinogenesis may be in part mediated through IL-1beta.
Uedo
Noriya
N
Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 3-3, Nakamichi 1-chome, Higashinari-ku, Osaka 537-8511, Japan. uedo-no@mc.pref.osaka.jp
Tatsuta
Masaharu
M
Iishi
Hiroyasu
H
Baba
Miyako
M
Yano
Hiroyuki
H
Ishihara
Ryu
R
Higashino
Koji
K
Ishiguro
Shingo
S
D000230:Adenocarcinoma / Q000139:chemically induced / Q000382:microbiology / Q000473:pathology; D000818:Animals; D002455:Cell Division; D004357:Drug Synergism; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D005756:Gastritis / Q000139:chemically induced / Q000382:microbiology; D016481:Helicobacter Infections / Q000139:chemically induced* / Q000150:complications; D016480:Helicobacter pylori; D007375:Interleukin-1 / Q000633:toxicity*; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D009361:Neoplasm Invasiveness; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000382:microbiology / Q000473:pathology
D007375:Interleukin-1; D018809:Proliferating Cell Nuclear Antigen; D008769:Methylnitronitrosoguanidine