Endogenous factors, as genetic predisposition, absorption, distribution and activation, influence the cell response to drugs. Although some antitumor drugs, such as cisplatin and vincristine are extensively used in the clinical treatment to induce apoptosis in cancerous cells, their mechanisms of action have not yet been fully understood. It has been suggested that many drugs promote the regression of cancer due to the increase of intracellular levels of free radicals, which could be responsible to activate the process of apoptosis. S cerevisiae cells have been used as an eukaryotic model to evaluate citotoxity of antitumor drugs because their growth could be related to cancerous (fermentative metabolism) or to normal cells (respiratory metabolism). In this work we evaluated the level of cisplatin citotoxicity in mutant strains of S. cerevisiae with specific deficiencies in antioxidant defense systems (glutathione, gsh, and cytoplasmatic superoxide dismutase, sod1). In the experiments, cells were grown either in a fermentative or respiratory medium and then exposed to 0.45 mM cisplatin up to 24h. In all strains tested, cisplatin inhibit growth and reduced cell viability. However, cells deficient in glutathione synthesis, showed to be more sensitive suggesting that glutathione may be involved in the process of cisplatin detoxification. Interesting enough the mutant sod1, which presented high survival rates when compared with its control and gsh1 mutant strains, showed the highest mitochondrial mutagenesis phenotype after cisplatin treatment. In addition, we observed that cells in respiratory metabolism acquire tolerance only after long time of exposure. Finally, results presented here by the sod1 and gsh1 mutants suggest that cisplatin can be greatly deleterious for eukaryotic cells if the antioxidant defense is not well developed.