Induction of apoptosis and mitosis inhibition by degraded DNA lipotransfection mimicking genotoxic drug effects

Genotoxic damage induces cell cycle arrest and/or apoptosis by activation o f p53 oncosuppressor protein. A number of anticancer drugs are genotoxic an d their damaging effect upon cells is mediated by this mechanism. Microinje ction of defined DNA species directly into nucleus has been reported previo usly to activate p53 and inhibit cell cycle. Here, we demonstrate that simp le addition of heterogeneous degraded DNA to cultured cells (Rat-l fibrobla sts) in combination with lipotransfecting agent DOTAP leads to apoptosis in duction and mitosis inhibition by a molecular mechanism which mimics that o f the cellular response to genotoxic anticancer agents. Indeed, both cellul ar effects induced by lipotransfected degraded DNA (essentially, heterogene ous small DNA fragments) are associated to p53 activation and modulated by two apoptosis-related genes, such as bcl-2 and c-myc, which also modulate t he apoptotic threshold to anticancer agents. Here we raise the hypothesis o f exogenous DNA segment lipotransfection as possible new tool for anticance r therapy. (C) Academy Press.