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| Determinants of O-6-alkylguanine-DNA alkyltransferase activity in human colon cancer |
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| Author(s): Gerson SL, Allay E, Vitantonio K, Dumenco LL |
| Source: CLINICAL CANCER RESEARCH Volume: 1 Issue: 5 Pages: 519-525 Published: MAY 1995 |
| Times Cited: 21 References: 38 |
| Abstract: The DNA repair protein O-6-alkylguanine-DNA alkyltransferase (alkyltransferase) repairs cytotoxic DNA O-6-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 O-6-benzylguanine to deplete alkyltransferase prior to therapy with a nitrosourea, triazine, or tetrazine. |
| Document Type: Article |
| Language: English |
| Reprint Address: Gerson, SL (reprint author), CASE WESTERN RESERVE UNIV, SCH MED, DEPT MED, BRB 3, 10900 EUCLID AVE, CLEVELAND, OH 44106 USA |
Addresses:
1. CASE WESTERN RESERVE UNIV, SCH MED, CTR CANC, BRB 3, CLEVELAND, OH 44106 USA |
| Publisher: AMER ASSOC CANCER RESEARCH, PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 |
| Subject Category: Oncology |
| IDS Number: TL080 |
| ISSN: 1078-0432 |
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