Sensitization of human colon tumour cell lines to carmustine by depletion ofO 6-alkylguanine-DNA alkyltransferase


In nine human colon tumour cell lines the relationship betweenO 6-alkylguanine-DNA alkyltransferase (O 6-AGT) activity and carmustine resistance was investigated. Three lines withO 6-AGT activity below 25 fmol/mg protein had carmustine ED50 values ranging from 5.0 μM to 11.9 μM; six lines displaying anO 6-AGT activity above 240 fmol/mg protein had ED50 values ranging from 28.9 μM to 69.5 μM. In lines with lowO 6-AGT activity, depletion of the repair protein byO 6-benzylguanine resulted in a marginal increase of carmustine cytotoxicity (sensitization factors less than 2). In the majority of cell lines with highO 6-AGT activity, pretreatment withO 6-benzylguanine resulted in a pronounced sensitization to carmustine. In one line, an optimal time schedule for sensitization of colon tumour cells byO 6-benzylguanine was assessed; continuous exposure toO 6-benzylguanine ≥16 h after carmustine exposure) was superior to short-term exposure limited to a period before carmustine treatment.

DOI: 10.1007/BF01366966

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@article{MagullSeltenreich1995SensitizationOH, title={Sensitization of human colon tumour cell lines to carmustine by depletion ofO 6-alkylguanine-DNA alkyltransferase}, author={Achim Magull-Seltenreich and W. Jens Zeller}, journal={Journal of Cancer Research and Clinical Oncology}, year={1995}, volume={121}, pages={225-229} }