Sensitization of human colon tumour cell lines to carmustine by depletion of O6-alkylguanine-DNA alkyltransferase
| Autor: | A. Magull-Seltenreich, W. J. Zeller |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Cancer Research
Methyltransferase Guanine Time Factors Drug Resistance Biology Streptozocin O(6)-Methylguanine-DNA Methyltransferase parasitic diseases medicine Tumor Cells Cultured Humans Cytotoxicity Sensitization Carmustine General Medicine Methyltransferases Molecular biology In vitro medicine.anatomical_structure Oncology Mechanism of action Biochemistry Cell culture Colonic Neoplasms medicine.symptom Drug Screening Assays Antitumor medicine.drug Alkyltransferase |
| Zdroj: | Journal of cancer research and clinical oncology. 121(4) |
| ISSN: | 0171-5216 |
| Popis: | In nine human colon tumour cell lines the relationship between O6-alkylguanine-DNA alkyltransferase (O6-AGT) activity and carmustine resistance was investigated. Three lines with O6-AGT activity below 25 fmol/mg protein had carmustine ED50 values ranging from 5.0 microM to 11.9 microM; six lines displaying an O6-AGT activity above 240 fmol/mg protein had ED50 values ranging from 28.9 microM to 69.5 microM. In lines with low O6-AGT activity, depletion of the repair protein by O6-benzylguanine resulted in a marginal increase of carmustine cytotoxicity (sensitization factors less than 2). In the majority of cell lines with high O6-AGT activity, pretreatment with O6-benzylguanine resulted in a pronounced sensitization to carmustine. In one line, an optimal time schedule for sensitization of colon tumour cells by O6-benzylguanine was assessed; continuous exposure to O6-benzylguanineor = 16 h after carmustine exposure) was superior to short-term exposure limited to a period before carmustine treatment. |
| Databáze: | OpenAIRE |
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