Formation and resealing of intercalator-induced DNA strand breaks in permeabilized L1210 cells without the stimulated synthesis of poly(ADP-ribose).

Abstract

DNA strand breaks produced by damaging agents such as x-ray generally stimulate poly(adenosine diphosphoribose) (ADP-R) synthesis in mammalian cells. DNA intercalating agents induce the formation of strand breaks which are unusual in that they are associated with tightly or covalently bound protein. In order to determine whether the intercalator-induced strand breaks are associated with poly-(ADP-R) synthesis, L1210 cells were treated with the intercalating agent, 4'-(9-acridinylamino)methanesulfon-m-anisidide. Poly(ADP-R) synthesis, measured by [3H]NAD incorporation following cell permeabilization, was enhanced in x-irradiated cells, but not in cells exposed to 4'-(9-acridinylamino)methanesulfon-m-anisidide at doses which produced equivalent strand breaks frequencies. The permeabilized cell system did not support DNA synthesis and x-ray-induced strand breaks did not reseal. The intercalator-induced strand breaks, however, resealed within 10 min. Hence, the strand breaks observed in intercalator-treated cells may not constitute DNA damage in the usual sense. The resealing of intercalator-induced DNA breaks in the absence of DNA or poly(ADP-R) synthesis is unique among chemical or physical agents which produce DNA scissions.