p53 and redox state in etoposide-induced acute myeloblastic leukemia cell death

We investigated whether p53, being a redox-sensitive protein, has a role in the responsiveness of AML cells to etoposide. Two subclones of the OCI/AML -2 cell line, the etoposide-sensitive (ES) and the etoposide-resistant (ER) , were used as models. Sensitivity to etoposide was measured by trypan blue and annexin V assays. Etoposide-induced peroxide formation was associated with the induction of cell death. Evident expression of mutated p53 was obs erved in both subclones in basal growth conditions as analysed by Western b lotting and flow cytometry. After etoposide exposure for up to 24 hours, so me nuclear accumulation of p53 was observed in the ER subclone, as analysed by Western blotting. The conformation of p53, however, was not changed fro m mutated toward wild-type during exposure in either of the subclones as an alysed by flow cytometry. In conclusion, etoposide-induced change in cellul ar redox state was associated with apoptosis, but was not a sufficient stim ulus for p53 to make its conformation active. Thus, mutated p53 seems to ha ve no role in etoposide-induced apoptosis. (C) 2001 Elsevier Science Ltd. A ll rights reserved.