Elevated levels of the pro-carcinogenic adduct, O(6)-methylguanine, in normal DNA from the cancer prone regions of the large bowel.
AffiliationCancer Research Campaign Section of Genome Damage and Repair, Paterson Institute for Cancer Research, Manchester, M20 9BX, UK. email@example.com
MetadataShow full item record
AbstractBACKGROUND: 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 <0. 01-0.94 and <0.01-0.151 micromol O(6)-MedG/mol deoxyguanosine for normal and tumour DNA, respectively. Levels of O(6)-MedG in normal, but not tumour, DNA from the proximal colon were lower than those found in DNA from either the sigmoid colon (p=0.03) or rectum (p=0. 05). When the analysis was restricted to samples that contained O(6)-MedG, similar results were obtained in that O(6)-MedG levels in normal DNA were lower in the proximal colon than in the sigmoid colon (p=0.04) or rectum (p=0.03). CONCLUSIONS: DNA alkylation varied within the large bowel possibly due to in situ NOC formation and was highest in areas of the colon and rectum where the highest incidence of large bowel tumours occurs, suggesting that DNA alkylation may play a role in the aetiology of colorectal cancer.
CitationElevated levels of the pro-carcinogenic adduct, O(6)-methylguanine, in normal DNA from the cancer prone regions of the large bowel. 2000, 47 (3):362-5 Gut
- Host determinants of DNA alkylation and DNA repair activity in human colorectal tissue: O(6)-methylguanine levels are associated with GSTT1 genotype and O(6)-alkylguanine-DNA alkyltransferase activity with CYP2D6 genotype.
- Authors: Povey AC, Hall CN, Badawi AF, Cooper DP, Guppy MJ, Jackson PE, O'Connor PJ, Margison GP
- Issue date: 2001 Aug 22
- Frequency of Ki-ras mutations and DNA alkylation in colorectal tissue from individuals living in Manchester.
- Authors: Jackson PE, Hall CN, Badawi AF, O'Connor PJ, Cooper DP, Povey AC
- Issue date: 1996 May
- Levels of the DNA adduct, N7-methyldeoxyguanosine, are associated with increased risk of failure of treatment of cervical intraepithelial neoplasia.
- Authors: Acladious NN, Harrison KL, Sutton CJ, Povey AC, Mandal D, Kitchener H
- Issue date: 2004 Jun
- Development and application of a sensitive and rapid immunoassay for the quantitation of N7-methyldeoxyguanosine in DNA samples.
- Authors: Harrison KL, Wood M, Lees NP, Hall CN, Margison GP, Povey AC
- Issue date: 2001 Mar
- N7-methyldeoxyguanosine levels in DNA isolated from cervical cytology samples are associated with smoking.
- Authors: Harrison KL, Khan NS, Dey P, Povey AC
- Issue date: 2006 Aug 15