O(6)-methyldeoxyguanosine in oesophageal DNA among individuals at high risk of oesophageal cancer.
A radioimmunoassay using monoclonal antibodies (MAb) against 0(6)-medGuo and 0(6)-etdGuo enabled the presence of these DNA adducts to be detected in human tissues. With this methodology and with 1 mg of hydrolysed DNA it is possible to detect approximately 25 fmol 0(6)-medGuo or 12.5 fmol 0(6)-etdGuo per mg DNA. The analysis comprised a total of 37 human tissue specimens derived from patients who underwent surgery for cancer of the oesophagus in Linxian County (People's Republic of China); for comparison 12 tissue samples obtained from hospitals in Europe were similarly analysed. Seventeen samples from Linxian County showed a level of 0(6)-medGuo ranging from 15 to 50 fmol/mg DNA, 10 showed higher levels up to 160 fmol/mg DNA, and the remaining 10 samples were below the limit of detection. All the tissue samples from Europe showed levels below 45 fmol 0(6)-medGuo/mg DNA, 7 being below the limit of detection. No 0(6)-etdGuo was detected in any of the samples. 0(6)-alkylguanine DNA alkyltransferase activity observed in tissue extracts from Linxian County ranged from 190 to 326 fmol (mean values) of 0(6)-medGuo removed per mg protein and lower values were obtained for the removal of 0(6)-etdGuo. The findings obtained using this approach appear promising in assessing the role of alkylating agents, e.g. nitrosamines, in the aetiology of human cancer.
D002681:China; D004247:DNA / Q000032:analysis*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D004938:Esophageal Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D004947:Esophagus / Q000378:metabolism; D005602:France; D005753:Gastric Mucosa / Q000378:metabolism; D005858:Germany; D006801:Humans; D008780:Methyltransferases / Q000378:metabolism; D009092:Mucous Membrane / Q000378:metabolism; D009602:Nitrosamines / Q000378:metabolism; D019853:O(6)-Methylguanine-DNA Methyltransferase; D011863:Radioimmunoassay; D012306:Risk
D009602:Nitrosamines; D004247:DNA; C015558:O(6)-methyl-2'-deoxyguanosine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D003849:Deoxyguanosine