Attenuation by methionine of monochloramine-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.
Helicobacter pylori appears to play a major role in the development of gastric cancer in humans. The mechanism behind the carcinogenic or co-carcinogenic effects of H. pylori has not been established. Ammonia, generated by urea from H. pylori, has been studied as a possible cause. However, the ammonia-monochloramine system has been shown to play a more important role in H. pylori-associated mucosal injury. Therefore, the effects of combined administration of monochloramine and methionine, singly or together, on the development of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in inbred Wistar rats. After receiving oral MNNG and regular chow pellet for 25 weeks, rats received regular chow pellets or chow pellets containing 20% ammonium acetate, and normal tap water or water containing 30 mM sodium hypochlorite, with or without a subcutaneous injection of methionine, until the end of the experiment (week 52). Treatment with both ammonium acetate and sodium hypochlorite, which produce monochloramine, significantly increased the incidence of gastric cancers in week 52, whereas the concomitant administration of methionine with ammonium acetate and sodium hypochlorite significantly attenuated such enhanced gastric carcinogenesis. Spectrophotometric examination revealed that methionine scavenged monochloramine. Our findings suggest that H. pylori-associated gastric carcinogenesis may be mediated by monochloramine.
Iseki
K
K
Department of Gastroenterology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.
Tatsuta
M
M
Iishi
H
H
Baba
M
M
Mikuni
T
T
Hirasawa
R
R
Yano
H
H
Uehara
H
H
Nakaizumi
A
A
D000818:Animals; D017209:Apoptosis; D002273:Carcinogens; D002455:Cell Division; D002700:Chloramines / Q000037:antagonists & inhibitors*; D008297:Male; D008715:Methionine / Q000494:pharmacology*; D008769:Methylnitronitrosoguanidine; D051381:Rats; D011919:Rats, Inbred Strains; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000473:pathology
D002273:Carcinogens; D002700:Chloramines; D008769:Methylnitronitrosoguanidine; D008715:Methionine; C030816:chloramine