As estimated by WHO, there are in the world about 1.1 billion overweight subjects, with a rapid increase in prevalence. Excess body weight is an important risk factor for the development of many chronic degenerative diseases such as Type II diabetes and the "metabolic syndrome" (Metabolic Syndrome, Mets). Whether people suffering from diabetes that those with Mets have a morbid condition characterized by hyperglycemia associated with hyperinsulinemia, hypertension and dyslipidemia. Recently, it has been suggested that high blood glucose concentrations can cause an increase in intracellular production of free radicals which is known to be capable of inducing damage to DNA in cells. More recently it has also been suggested that high concentrations of glucose are able to increase the susceptibility of DNA to genotoxic effects of xenobiotic. The aim of this work was to verify the hypothesis that high concentrations of glucose added to the medium of hepatoma human cells (HepG2) are able to change the susceptibility to the same genotoxic compounds and investigate if antioxidant could restore normal homeostasis. To this end, HepG2 cells were cultured for 24 hours (37 Â°C, 5% CO2) in the presence of scalar glucose concentrations (1; 2,5; 5 and 10 g/l) and then treated for 4 hours with 4-nitroquinoline N-oxide (4NQO) in presence and absence of TroloxÂ®. The extent of damage to DNA was evaluated using comet test in alkaline conditions. The results showed that treatment with high concentrations of glucose did not alter the levels of primary DNA damage, while the co-exposure with 4NQO increase levels of damage depending on the concentration of glucose. The results obtained in this preliminary approach suggest that the condition of hyperglycemia favors an increased susceptibility of DNA to genotoxic insults and the used oxidant inhibitors suppress, even not completely, the intracellular generation of reactive oxygen species induced by high glucose.