Involvement of thiols in gastric cancer induced by N-methyl-N'-nitro-N-nitrosoguanidine: biochemical and autoradiographic studies
Kleihues, P.; Wiestler, O.D.
Iarc Scientific Publications 57: 603-608
1984
ISSN/ISBN: 0300-5038 PMID: 6533053 Document Number: 228600
Chronic administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water causes a high incidence of carcinomas of the glandular stomach in rats (Sugimura & Fujimura, 1967). Following a single oral dose of [14C-methyl]-MNNG (80 mg/L; 2.5 mg/kg b.w.), the extent of DNA methylation in the glandular stomach was 9 and 21 times higher than in forestomach and oesophagus, respectively. These differences were found to correlate with regional variations in the concentration of cellular thiols, which are known to accelerate the heterolytic decomposition of MNNG. When [14C-methyl]-MNNG was given intragastrically together with the thiol-blocking agent, N-ethylmaleimide, covalent binding of 14C-radioactivity to forestomach, glandular stomach and duodenum was almost completely abolished.