Determinants of O(6)-alkylguanine-DNA alkyltransferase activity in normal and tumour tissue from human colon and rectum.
AffiliationCancer Research Campaign, Section of Genome Damage and Repair, Paterson Institute for Cancer Research, Manchester, UK. firstname.lastname@example.org
MetadataShow full item record
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.
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. Cancer
JournalInternational Journal of Cancer.
- 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
- Longitudinal variation in O(6)-alkylguanine DNA-alkyltransferase activity in the human colon and rectum.
- Authors: Lees NP, Harrison KL, Hill E, Hall CN, Margison GP, Povey AC
- Issue date: 2002 Jul 15
- Low O6-alkylguanine DNA-alkyltransferase activity in normal colorectal tissue is associated with colorectal tumours containing a GC-->AT transition in the K-ras oncogene.
- Authors: Jackson PE, Hall CN, O'Connor PJ, Cooper DP, Margison GP, Povey AC
- Issue date: 1997 Jul
- Determinants of O6-alkylguanine-DNA alkyltransferase activity in human colon cancer.
- Authors: Gerson SL, Allay E, Vitantonio K, Dumenco LL
- Issue date: 1995 May
- Quantitative immunohistochemical estimates of O6-alkylguanine-DNA alkyltransferase expression in normal and malignant human colon.
- Authors: Zaidi NH, Liu L, Gerson SL
- Issue date: 1996 Mar