Genotoxic and anti-proliferative effects of aminoguanidine on gamma-irradiated MCF-7 breast cancer cells

Abstract

The intracellular production of nitric oxide is studied as a relevant phenomenon in exposure to ioniz-ing radiation. There is evidence of local nitric oxide production in solid tumors. The study evaluated the effects of the administration of aminoguanidine, a selective inhibitor of an isoform of nitric oxide synthase on the frequency of genotoxic damage, loss of clonogenic potential and induction of cytotoxicity after ex-posure of human breast tumor (MCF7) cells to ionizing radiation in radiotherapeutic doses. Cells were treated with aminoguanidine (1 or 2 mM) and irradiated by gamma radiation at doses between 0.5 and 8Gy. In cultures treated with 1 mM, we observed increased cytotoxicity and genotoxicity, and reduction of the clonogenic potential of the colonies. Alternatively, 2 mM aminoguanidine produced the opposite effect, apparently protecting cultures from the effects of exposures. The experiments suggested that the admin-istration of aminoguanidine may reduce the in vitro radiosensitivity of tumors due to the increase of the frequency of genotoxic damage.