06-Methyldeoxyguanosine in oesophageal dna among individuals at high risk of oesophageal cancer
Abstract
A radioimmunoassay using monoclonal antibodies (MAb) against 06-medGuo and 06-etdGuo enabled the presence of these DNA adducts to be detected in human tissues. With this methodology and with I mg of hydrolysed DNA it is possible to detect approximately 25 fmol 06-medGuo or 12.5 fmol 06-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 06-medGuo ranging from 15 to SO 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 06-medGuo/mg DNA, 7 being below the limit of detection. No 06-etdGuo was detected in any of the samples. 06-alkylguanine DNA alkyltransferase activity observed in tissue extracts from Linxian County. ranged from 190 to 326 fmol (mean values) of 06 medGuo removed per mg protein and lower values were obtained for the removal of 06-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.
