IDENTIFICATION IN RAT STOMACH MUCOSAE OF A CELL-POPULATION CHARACTERIZED BY A DEFICIENCY FOR THE REPAIR OF O-6-METHYLDEOXYGUANOSINE FROM DNA

Immunohistochemical studies have been used to show the time course for the cell-specific methylation of DNA in the upper gastrointestinal tr act of rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), The doses used were 1, 5, 25 and 50 mg MNNG/kg (i.g.) and tissue sampl es were analysed at intervals of from 1 to 192 h after treatment, Rela tively little reaction with nuclear DNA was observed in the forestomac h and still less in the oesophagus. Reaction with DNA was most extensi ve in the corpus, pylorus and the duodenum, reaching a peak of stainin g intensity between 2 and 4 h and then declining progressively thereaf ter, Staining for the presence of O-6-methyldeoxyguanosine (O-6-MedG) in DNA was highly selective and tended to occur in the nuclei of the b asal cells of the oesophagus and forestomach and in the cells of the l umenal border of the glands and villi of the corpus, pylorus and duode num. There were also areas, 5-15 glands apart where staining for O-6-M edG in the corpus and pylorus extended as far down as the basal mucosa . From 12 h after MNNG treatment, in the corpus and pylorus, a band of strongly methylated cells became apparent about 3-6 cells deep from t he lumen and remained identifiable up to 168 h after treatment with th e higher doses. These cells, which apparently have a very low O-6-MedG repair capacity, are stationary (i.e. not part of the escalator) and are located in the mesenchymal tissue elements as demonstrated by stai ning of serial sections with cytokeratin or vementin. The significance of this population of cells is unknown.