Elevated levels of the pro-carcinogenic adduct, O(6)-methylguanine, in normal DNA from the cancer prone regions of the large bowel

BACKGROUND: The pro-mutagenic lesion O(6)-methyldeoxyguanosine (O(6)-MedG), a marker of exposure to many N-nitroso compounds (NOC), can be detected in normal and tumour DNA isolated from colorectal tissue. The biological significance of this exposure is, as yet, unknown but in situ NOC formation is bacterially catalysed suggesting that NOC formation and potentially DNA alkylation will vary throughout the large bowel. AIMS: To determine if O(6)-MedG levels in colorectal DNA vary within the large bowel. PATIENTS: We studied 62 men and women undergoing surgery for colorectal tumours in the north west of England. METHODS: O(6)-MedG levels were measured in paired normal and tumour DNA samples. DNA was digested to nucleosides, fractionated by HPLC, and purified O(6)-MedG quantified by a radioimmunoassay. RESULTS: O(6)-MedG was detected in 27 out of a total of 62 (43%) normal DNA samples and in 30 of 58 (52%) tumour DNA samples: it was present at concentrations of