O6-Methylguanine-DNA transmethylase activity in extracts of human gastric mucosa

In view of the possible involvement of N-nitroso compounds in the etiology of gastric carcinoma in man, we have examined the abilities of extracts of human gastric mucosa for the removal from DNA of O6-methylguanine, the primary precarcinogenic lesion induced in DNA by methylating carcinogenic N-nitroso compounds. We find that all 20 specimens examined (including 14 non-neoplastic and 6 neoplastic) possess significant activity, removing on average 0.73 +/- 0.06 (s.e.m.) pmol O6-methylguanine per mg protein in the extract. This activity, which has the characteristics of an O6-methylguanine-DNA-transmethylase, while exhibiting wide interindividual variations, shows no significant differences between the groups of normal and of neoplastic tissues or between the groups of non-neoplastic tissues obtained from individuals with benign or with malignant gastric disease. It is estimated that the average O6-methylguanine-removing capacity of the cells of normal gastric mucosa (calculated as 166 000 +/- 26 000 (s.e.m.) molecules per cell) greatly exceeds the extent of DNA damage likely to be caused by gastric-juice N-nitroso compounds.