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0 6 ‐Methyldeoxyguanosine in oesophageal dna among individuals at high risk of oesophageal cancer
Author(s) -
Umbenhauer D.,
Wild C. P.,
Montesano R.,
Saffhill R.,
Boyle J. M.,
Huh N.,
Kirstein U.,
Thomale J.,
Rajewsky M. F.,
Lu S. H.
Publication year - 1985
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910360607
Subject(s) - dna , radioimmunoassay , detection limit , microbiology and biotechnology , biology , cancer , medicine , chemistry , biochemistry , chromatography , genetics
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 I 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 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 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.