1. ¹Department of Gastroenterology, Charité-Universitaetsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
2. ²Department of Hematology, Charité-Universitaetsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany
3. ³Department of Clinical and Molecular Oncology, Charité, Campus Berlin-Buch, Berlin, Germany

Correspondence: Dr C Hanski, Department of Gastroenterology, Charité-Universitaetsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. E-mail: christoph.hanski@charite.de

Received 14 February 2005; Revised 15 June 2005; Accepted 19 July 2005; Published online 19 September 2005.

Abstract

Knowledge of the type of biological reaction to chemotherapy is a prerequisite for its rational enhancement. We previously showed that irinotecan-induced DNA damage triggers in the HCT116p53^wt colon carcinoma cell line a long-term cell cycle arrest and in HCT116p53^-/- cells apoptosis (Magrini et al., 2002). To compare the contribution of long-term cell cycle arrest and that of apoptosis to inhibition of cell proliferation after irinotecan-induced DNA damage, we used this isogenic system as well as the cell lines LS174T (p53^wt) and HT-29 (p53^mut). Both p53^wt cell lines responded to damage by undergoing a long-term tetraploid G1 arrest, whereas the p53^mut cell lines underwent apoptosis. Cell cycle arrest as well as apoptosis caused a similar delay in cell proliferation. Irinotecan treatment also induced in mouse tumours derived from the p53^wt cell lines a tetraploid G1 arrest and in those derived from the p53-deficient cell lines a transient G2/M arrest and apoptosis. The delay of tumour growth was in the same range in both groups, that is, arrest- and apoptosis-mediated tumour growth inhibition was comparable. In conclusion, cell cycle arrest as well as apoptosis may be equipotent mechanisms mediating the chemotherapeutic effects of irinotecan.