DNA induces apoptosis in electroporated human promonocytic cell line U937

Experimental gene transfer has permitted a wide variety of studies on gene regulation and function. However, possible effects of the introduced DNA on cellular metabolism are not well understood. Here we demonstrated that int roduction of DNA into a promonocytic cell line, U937, by electroporation ca used extensive cell death. The toxicity of DNA was concentration-dependent. Various DNAs including plasmid and genomic: DNAs all caused cell death, in dicating that the toxicity is nucleotide sequence-independent. DNA-induced cell death was associated with internucleosomal DNA. fragmentation, a decre ase in cell size, and a considerable proportion of cells outside cell cycle . From these results, we concluded that cells died by apoptosis. Our findin gs have experimental implication for an important issue concerning the inte rpretation of experiments using gene transfer. In addition, we propose that our observed phenomenon may be relevant to an important immune defense mec hanism in monocytes/macrophages that facilitates a response to certain vira l infections. (C) 2000 Academic Press.