The DNA repair
protein O6-alkylguanine-DNA
alkyltransferase (
alkyltransferase) repairs cytotoxic
DNA O6-alkylguanine adducts induced by the nitrosoureas,
triazines, and tetrazines. In this study, we determined whether there was a relationship between
alkyltransferase activity in
colon cancer and that of adjacent normal mucosa, and whether there were demographic patient characteristics which correlated with
alkyltransferase expression in either tissue.
Alkyltransferase activity and expression of the
alkyltransferase gene, MGMT, were measured in 49 paired primary
colon cancer samples and adjacent normal appearing mucosa.
Alkyltransferase activity was found in all samples. The mean activity was higher in the
tumor than the mucosa (r = 0.374, P < 0. 01), although the low correlation coefficient suggested that multiple factors influence the
alkyltransferase activity. MGMT
mRNA could also be detected in all samples and was highly correlated with
alkyltransferase activity (r = 0.64, P < 0.001). No correlation was found between
alkyltransferase activity and age, or gender of the patient, or location of the
tumor, although activity tended to be higher in patients with lower stage disease. Thus,
alkyltransferase activity is present in most, if not all,
colon cancer samples, suggesting that it could play an important role in chemotherapeutic resistance of human
colon cancer. Patients with
colon cancer would appear to be prime candidates for studies utilizing
O6-benzylguanine to deplete
alkyltransferase prior to
therapy with a nitrosourea,
triazine, or tetrazine.