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    Determinants of O(6)-alkylguanine-DNA alkyltransferase activity in normal and tumour tissue from human colon and rectum.

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    Authors
    Povey, Andrew C
    Hall, C Nicholas
    Cooper, Donald P
    O'Connor, Peter J
    Margison, Geoffrey P
    Affiliation
    Cancer Research Campaign, Section of Genome Damage and Repair, Paterson Institute for Cancer Research, Manchester, UK. andy.povey@man.ac.uk
    Issue Date
    2000-01-01
    
    Metadata
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    Abstract
    O(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.
    Citation
    Determinants 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
    Journal
    International Journal of Cancer.
    URI
    http://hdl.handle.net/10541/86143
    PubMed ID
    10585585
    Type
    Article
    Language
    en
    ISSN
    0020-7136
    Collections
    All Paterson Institute for Cancer Research

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