Occupational risk assessment of genotoxicity and oxidative stress in workers handling anti-neoplastic drugs during a working week.

Twenty pharmacists and nurses handling anti-neoplastic drugs in a hospital were monitored during a working week, from Monday to Friday, in the morning (only on Monday) and afternoon (all days). Genotoxicity was analysed by the comet assay and the micronucleus (MN) test, while oxidative stress was analysed in serum by thiobarbituric acid reactive substances (TBARS) and by measurements of the antioxidant enzymes superoxide dismutase (Sod) and catalase (Cat). The exposed workers presented increased DNA damage levels by the comet assay as compared to the controls. The comet assay results have also shown significant positive correlation with the day of the week and with alcohol consumption. MN frequency was significantly higher in the exposed workers and presented noteworthy correlation with age and working time. In the oxidative stress parameters, only Cat presented a significant increase in the exposed group, considering all the samplings. However, TBARS data showed interesting results, considering the different sampling times; the exposed group presented a significant correlation with the working days and significantly higher results on Friday as compared to the controls and Monday morning. Monitoring occupational risk during a longer time, e.g. during a working week as done in this study, introduces additional aspects of risk behaviour, which can improve risk management. This study demonstrates the usefulness of evaluating oxidative stress also in genotoxic risk assessment since both events often result from the same factors.

DNA damage in bipolar disorder.

Bipolar disorder (BD) is a prevalent, chronic, severe, and highly disabling psychiatric disorder that is associated with increased morbidity and mortality due to general medical conditions. There is an emerging body of evidence correlating chronic medical conditions with DNA damage. The present study was designed to assess DNA damage in BD patients using the comet assay (CA). Thirty-two bipolar-I outpatients diagnosed using the Structured Clinical Interview for DSM-IV were matched with 32 healthy volunteers. Manic and depressive symptoms were assessed using the Young Mania Rating Scale and the Hamilton Depression Rating Scale, respectively. Peripheral blood samples were collected and a standard protocol for CA preparation and analysis was performed. The present study showed that BD outpatients present an increased frequency of DNA damage relative to controls. The frequency of DNA damage correlated with the severity of symptoms of depression and mania.

Reduction of Na(+),K(+)-ATPase activity in hippocampus of rats subjected to chemically induced hyperhomocysteinemia.

Hyperhomocysteinemia occurs in homocystinuria, an inherited metabolic disease clinically characterized by thromboembolic episodes and a variable degree of neurological dysfunction whose pathophysiology is poorly known. In this study, we induced elevated levels of homocysteine (Hcy) in blood (500 microM), comparable to those of human homocystinuria, and in brain (60 nmol/g wet tissue) of young rats by injecting subcutaneously homocysteine (0.3-0.6 micromol/g of body weight) twice a day at 8-hr intervals from the 6th to the 28th postpartum day. Controls received saline in the same volumes. Na(+),K(+)-ATPase and Mg(2+)-ATPase activities were determined in the hippocampus of treated Hcy- and saline-treated rats. Chronic administration of Hcy significantly decreased (40%) Na(+),K(+)-ATPase activity but did not alter Mg(2+)-ATPase activity. Considering that Na(+),K(+)-ATPase plays a crucial role in the central nervous system, our results suggest that the brain dysfunction found in homocystinuria may be related to the reduction of brain Na(+),K(+)-ATPase activity.