Effects of an inhibitor of nitric oxide production on cell cycle and micronucleus frequency in irradiated human breast adenocarcinoma cells

Abstract

Breast adenocarcinomas ar e the most frequent malignant tumor (about 25% of cases), and its malignant outcome causes about 15% of all deaths of women with cancer. The production of nitric oxide (NO) by isoforms of nitric ox ide synthases (NOS’s) are related to increased malignancy a nd stimuli to metastatic progression of breast adenocarcinomas, but its presence in irradiated cells can lead to higher frequencies of DNA damage. The work used aminoguanidine, an inhibitor of isof orm 2 of NOS (NOS 2) to treat human breast cancer cells (MCF 7) in non toxic concentrations (1 and 2mM) before exposure to gamma irradiation 60 Co) to assess if reduction of intracellular NO can protect from, or induce radio induced cell damage, cell cycle disruption or death. Cells were treated and irradiated at 0, 0.5, 1, 2, 4 or 8Gy . A dministration of aminoguanidine arrest ed the cell cycle in the synthesis (S) phase, altering the DNA repair capacity of cells. T he higher concentration (2mM) led to less genotoxic damage (about 50%) in cells irradiated at 8Gy as obse rved using micronucleus scoring by flow cytometry. Alternatively, 1mM of aminoguanidin e increased genotoxic damage and induced a less significant increase of S phase cells. Despite the findings, no significant alterations in cell proliferation rates were o bserved. Finding s showed that aminogua ni dine can modulate radio induced ef fects on cells.