Methyl methanesulfonate and hydrogen peroxide differentially regulate p53 accumulation in hepatoblastoma cells

Genotoxic chemicals not only damage cellular DNA, but may also induce cell apoptosis if they are lethal to the cell. p53, Bcl-2 and Bax play important roles in the regulation of genotoxic chemical induced cell apoptosis. Sinc e the mechanisms by which cellular DNA damaged by different DNA-damaging ch emicals may not be the same, we studied the involvement of p53, Bcl-2 and B ax in apoptosis induced by methyl methanesulfonate (MMS) and hydrogen perox ide (H2O2). H2O2 damages DNA by free radical generation and MMS damages DNA by DNA methylation. At non-lethal doses, both H2O2 and MMS induced high le vel of p53 protein accumulation. Nevertheless, while the amount of p53 prot ein increased with the dose of MMS and the occurrence of apoptotic cell dea th events, H2O2 doses that induce cell apoptosis attenuated the p53 protein accumulation level. Lethal MMS treatment also increased Bax, but not Bcl-2 expression, whereas in H2O2 induced apoptosis, the level of both Bcl-2 and Bax declined. These results indicate that toxic chemicals differentially r egulate the accumulation of p53 protein. Thus, the pathways of toxic chemic als induced cell apoptosis are different and independent. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.