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

Abstract

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

3 Figures and Tables

Statistics

0100200'97'99'01'03'05'07'09'11'13'15'17
Citations per Year

351 Citations

Semantic Scholar estimates that this publication has 351 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@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} }