Kyrtopoulos S A, Vrotsou B, Golematis B, Bonatsos M, Lakiotis G
Carcinogenesis. 1984 Jul;5(7):943-7. doi: 10.1093/carcin/5.7.943.
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.
鉴于N-亚硝基化合物可能与人胃癌的病因有关，我们检测了人胃黏膜提取物从DNA中去除O6-甲基鸟嘌呤的能力，O6-甲基鸟嘌呤是甲基化致癌性N-亚硝基化合物在DNA中诱导产生的主要致癌前病变。我们发现，所检测的所有20个标本（包括14个非肿瘤性标本和6个肿瘤性标本）均具有显著活性，提取物中每毫克蛋白质平均能去除0.73±0.06（标准误）皮摩尔的O6-甲基鸟嘌呤。这种具有O6-甲基鸟嘌呤-DNA-转甲基酶特征的活性，虽然个体间差异很大，但在正常组织和肿瘤组织组之间，或从患有良性或恶性胃病的个体获得的非肿瘤组织组之间，均未显示出显著差异。据估计，正常胃黏膜细胞的平均O6-甲基鸟嘌呤去除能力（计算为每个细胞166000±26000（标准误）个分子）大大超过了胃液中N-亚硝基化合物可能造成的DNA损伤程度。
