Micronucleus (MN) assay constitutes a valuable surrogate to the chromosome aberration technique for in vitro testing of the genotoxicity of substances. As test substances, two peptidic compounds (DOTATATE and Ubiquicidin) used in nuclear medicine, were tested for in vitro cytotoxicity and genotoxicity in CHO-K1 cells. None of the compounds showed detectable cytotoxicity (0.5-7.3 ng/mL for DOTATATE and 0.3-4.5 ng/mL for UBI), genotoxicity (0.72, 7.2 and 72.0 ng/ml for DOTATATE and 0.45, 4.5 and 45.0 ng/mL for UBI) or cell cycle changes as compared to untreated controls at the concentrations tested. Statistical analysis showed good concordance between two independent analysts. The results corroborate the notion of the safety of the compounds and present improvements of the in vitro MN assay when performed in a pre-clinical trial context that increase the throughput of small-to-medium testing facilities as an alternative to high content screening systems.

Dias do centro de Radiofarmácia. Ao Laboratório Biosintesis Ltda., em especial à Dra. Fabiana Medeiros da Silva e à MSc. Tatiana F. da Cunha pela parceria inestimável no desenvolvimento do projeto. A todo o Centro de Biotecnologia, pela ajuda prestada dentro e fora da rotina do laboratório.

The intracellular production of nitric oxide is studied as a relevant phenomenon in exposure to ionizing 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 exposure 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 administration of aminoguanidine may reduce the in vitro radiosensitivity of tumors due to the increase of the frequency of genotoxic damage.