Moreover, many studies have assessed the risk of workers

who handle anti-neoplastic drugs [1–15]. The health hazard for medical personnel administering these drugs is a major concern as these drugs are classified as potentially carcinogenic, mutagenic or teratogenic [16]. Exposure can occur mainly to hands and sporadically to other body parts as well. As these drugs directly or indirectly affect DNA, not only the cancer patients but also the medical personnel chronically handling these drugs are at a higher risk for acquiring DNA damage. Cardiotoxicity is a major complication of anticancer drugs, including anthracyclines and 5-fluorouracil (5FU) [17–20]. Anthracyclines are the best studied among the anticancer drugs with established cardiotoxicity [21, 22]. They produce cardiac toxicity Navitoclax manufacturer accompanied selleck kinase inhibitor by an increase in myofibrillar disarray that is mediated by the signaling function of neuregulin 1 [23]. In addition, anthracyclines induce mitochondrial apoptosis pathways and free radical production [24,

25]. The mechanisms by which other chemotherapy drugs produce cardiovascular toxicities have also been investigated. 5-FU, a widely used chemotherapeutic, has direct toxic effects on vascular endothelium that involves endothelial nitric oxide (NO) synthase and leads to coronary spasms and endothelium-independent vasoconstriction via protein kinase C [26–32]. Therefore, also for this latter drug unexpected cardiotoxicity can occur above all in old patients who have often associated co-morbidities

and can be defined frail patients. Above all in this latter category of patients, the understanding of the molecular mechanisms at the basis of the cardiotoxic effects induced by anti-cancer agents could be useful in order to determine possible pharmacological strategies in order to prevent this deleterious side effect. Moreover, the toxic effects on normal cells (cardiocytes) could differ from those induced in cancer cells (i.e.: colon cancer cells) and this could allow the Epothilone B (EPO906, Patupilone) use of cardioprotective agents without affecting the anti-cancer properties of 5-FU. It has also to be considered that an unexpected high risk of exposure to 5-FU was recently found in a population of workers of South Italy involved in the manipulation of cytostatic agents [33]. In the present study, we have evaluated the cardiotoxic effects of 5-FU and DOXO on rat cardiocytes (H9c2) [30] and a human colon adenocarcinoma (HT-29) cell line, already reported to be sensitive to 5-FU, for the study of the cell death pathways induced in cardiac and colon cancer cells. Materials and methods Materials RPMI, DMEM, and FBS were purchased from Flow Laboratories (Milan, Italy). Tissue culture plasticware was from Microtech (Naples, Italy). Rabbit antiserum raised against caspase 9 and monoclonal antibodies (mAb) raised against caspase 3 and caspase 7 were purchased from Enzo Life Sciences (Florence, Italy).