Occupational exposure to antineoplastic drugs: an italian network of oncological hospitals for the biomonitoring of workers by buccal micronucleus cytome assay and the detection of workplace contamination

Introduction: An Italian Network of 7 Oncological Hospitals has been established to evaluate cyto-genotoxic effects on workers handling Antineoplastic Drugs (AD) by Buccal Micronucleus Cytome assay as biomarker of early effect and to monitor workplace contamination using the same procedures and method of analysis. Methods: We enrolled 169 workers handling mixtures of AD (mean age 42±11) and 126 controls (mean age 43±10) to evaluate DNA damage (detecting cells with MN and nuclear buds), cytokinesis defect/arrest (by binucleated cells), advanced stage of necrosis and apoptosis (by karyolytic cells) and early apoptosis (by condensed chromatin). Subjects with micronucleated cells frequency exceeding a fixed cut-off value (1.5‰) were considered positive to MN assay. We detected AD contamination performing workplace and personal monitoring of four drugs (Gemcitabine, Ifosfamide, Cyclofosfamide and 5-Fluorouracil) analysed by high-performance liquid chromatographic method coupled with a tandem mass spectrometer (UHPLC MS/MS). Results: We found differences in the mean values of the BMCyt parameters between exposed and controls particularly for the positivity to MN with a higher percentage found among the administrators vs the preparators. We found low levels, but still detectable, of contamination in all the monitored workplaces with higher concentrations in the workplaces of administration. Discussion The biomonitoring and workplace monitoring results have demonstrated to be correlated since preparators showed lower cyto-genotoxic damage, in agreement with the lower levels of AD contamination found where the preparation had occurred Conclusions: The BMCyt assay was confirmed to be a suitable biomarker for biomonitoring of workers handling AD due to its sensitivity and non-invasiveness.