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dc.contributor.authorPovey, Andrew C
dc.contributor.authorHall, C Nicholas
dc.contributor.authorCooper, Donald P
dc.contributor.authorO'Connor, Peter J
dc.contributor.authorMargison, Geoffrey P
dc.date.accessioned2009-11-13T14:51:29Z
dc.date.available2009-11-13T14:51:29Z
dc.date.issued2000-01-01
dc.identifier.citationDeterminants of O(6)-alkylguanine-DNA alkyltransferase activity in normal and tumour tissue from human colon and rectum. 2000, 85 (1):68-72 Int. J. Canceren
dc.identifier.issn0020-7136
dc.identifier.pmid10585585
dc.identifier.urihttp://hdl.handle.net/10541/86143
dc.description.abstractO(6)-Alkylguanine-DNA-alkyltransferase (ATase) is an important modulator of alkylating agent-induced toxicity and carcinogenicity, but those factors which influence the expression of this repair protein in human tissues are poorly characterised. In this study, we have determined ATase levels in macroscopically normal and tumour tissues from 76 individuals with benign or malignant colorectal disease. All tissue samples had detectable ATase activity, with values ranging from 35 to 451 fmol/mg protein. ATase activity in normal rectal tissue was significantly higher than that in normal tissue from the sigmoid colon (148 +/- 76 vs. 100 +/- 40 fmol/mg protein, p = 0.01), whereas ATase levels within different regions of the colon (proximal vs. sigmoid colon) were similar. In normal tissue, inter-individual variation in ATase activity was 4-fold in the colon and 6-fold in the rectum, whereas in tumour tissue the corresponding figures were approx. 13.0- and 7-fold, respectively. There was no detectable difference in normal tissue ATase activity between individuals with benign or malignant disease of the colon. Normal and tumour tissue ATase activities were strongly correlated in the sigmoid colon (r = 0.80) and rectum (r = 0.59) but not the caecum (r = -0.03). In a multivariate analysis, ATase activity in normal colon tissue increased with age (p = 0.01) and current smoking (p = 0.06), whereas tumour ATase activity increased only with use of anti-histamines (p = 0.05). In rectal tumour tissue, activity decreased with age (p = 0.05) and use of anti-muscarinic medications (p = 0.01): in normal rectal tissue, no modulating factors were identified.
dc.language.isoenen
dc.subjectColonic Canceren
dc.subjectRectal Canceren
dc.subjectSigmoid Canceren
dc.subject.meshAge Factors
dc.subject.meshAged
dc.subject.meshBenzodiazepines
dc.subject.meshColon
dc.subject.meshColonic Diseases
dc.subject.meshColonic Neoplasms
dc.subject.meshEnzyme Activation
dc.subject.meshFemale
dc.subject.meshHistamine H1 Antagonists
dc.subject.meshHumans
dc.subject.meshLinear Models
dc.subject.meshMale
dc.subject.meshMultivariate Analysis
dc.subject.meshMuscarinic Antagonists
dc.subject.meshMutation
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase
dc.subject.meshRectal Neoplasms
dc.subject.meshRectum
dc.subject.meshReference Values
dc.subject.meshSigmoid Neoplasms
dc.subject.meshSmoking
dc.titleDeterminants of O(6)-alkylguanine-DNA alkyltransferase activity in normal and tumour tissue from human colon and rectum.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign, Section of Genome Damage and Repair, Paterson Institute for Cancer Research, Manchester, UK. andy.povey@man.ac.uken
dc.identifier.journalInternational Journal of Cancer.en
html.description.abstractO(6)-Alkylguanine-DNA-alkyltransferase (ATase) is an important modulator of alkylating agent-induced toxicity and carcinogenicity, but those factors which influence the expression of this repair protein in human tissues are poorly characterised. In this study, we have determined ATase levels in macroscopically normal and tumour tissues from 76 individuals with benign or malignant colorectal disease. All tissue samples had detectable ATase activity, with values ranging from 35 to 451 fmol/mg protein. ATase activity in normal rectal tissue was significantly higher than that in normal tissue from the sigmoid colon (148 +/- 76 vs. 100 +/- 40 fmol/mg protein, p = 0.01), whereas ATase levels within different regions of the colon (proximal vs. sigmoid colon) were similar. In normal tissue, inter-individual variation in ATase activity was 4-fold in the colon and 6-fold in the rectum, whereas in tumour tissue the corresponding figures were approx. 13.0- and 7-fold, respectively. There was no detectable difference in normal tissue ATase activity between individuals with benign or malignant disease of the colon. Normal and tumour tissue ATase activities were strongly correlated in the sigmoid colon (r = 0.80) and rectum (r = 0.59) but not the caecum (r = -0.03). In a multivariate analysis, ATase activity in normal colon tissue increased with age (p = 0.01) and current smoking (p = 0.06), whereas tumour ATase activity increased only with use of anti-histamines (p = 0.05). In rectal tumour tissue, activity decreased with age (p = 0.05) and use of anti-muscarinic medications (p = 0.01): in normal rectal tissue, no modulating factors were identified.


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