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O(6)-methyldeoxyguanosine in oesophageal DNA among individuals at high risk of oesophageal cancer.

Abstract
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.
AuthorsD Umbenhauer, C P Wild, R Montesano, R Saffhill, J M Boyle, N Huh, U Kirstein, J Thomale, M F Rajewsky, S H Lu
JournalInternational journal of cancer (Int J Cancer) Vol. 36 Issue 6 Pg. 661-5 (Dec 15 1985) ISSN: 0020-7136 [Print] United States
PMID4066072 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Nitrosamines
  • DNA
  • O(6)-methyl-2'-deoxyguanosine
  • Methyltransferases
  • O(6)-Methylguanine-DNA Methyltransferase
  • Deoxyguanosine
Topics
  • China
  • DNA (analysis)
  • Deoxyguanosine (analogs & derivatives, analysis)
  • Esophageal Neoplasms (chemically induced, metabolism)
  • Esophagus (metabolism)
  • France
  • Gastric Mucosa (metabolism)
  • Germany
  • Humans
  • Methyltransferases (metabolism)
  • Mucous Membrane (metabolism)
  • Nitrosamines (metabolism)
  • O(6)-Methylguanine-DNA Methyltransferase
  • Radioimmunoassay
  • Risk

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