Buccal micronucleus cytome assay to evaluate cyto-genotoxic effects of occupational exposure to antineoplastic drugs: application on a large sample size of workers furnished by an Italian network of oncological hospitals

Many antineoplastic drugs (ADs) used to treat cancer are characterized by the non-selective effect representing a possible cause of health effects in exposed workers. We established an Italian Network of seven Oncological Hospitals with the aim to evaluate, on a large size sample of workers, cyto-genotoxic effects by a sensitive and non-invasive biomarker also detecting workplace and personal contamination. We performed Buccal Micronucleus Cytome (BMCyt) assay on 200 workers handling ADs and 150 controls. AD contamination was detected performing workplace and personal monitoring of Gemcitabine, Ifosfamide, Cyclofosfamide and 5-Fluorouracil, using UHPLC MS/MS. We found in all the exposed group higher mean values of cells with micronucleus (MN‰), higher percentage of positivity to MN (subjects with micronucleated cells frequency exceeding a fixed cut-off value (1.5‰)), higher frequency of binucleated cells, broken eggs and total anomalies than in the controls. Taking into account the tasks (preparation, administration in Day Hospital and wards, administration in room operator and disposal), only preparators and administrators showed higher MN‰ frequency than in controls, whereas each task group showed a similar higher percentage of MN positives than in controls. We found low levels, but still detectable, of contamination in all the monitored workplaces. This study demonstrated induction of genotoxicity and of cytokinesis defect/arrest in buccal cells of workers handling antineoplastic drugs. The BMCyt assay was demonstrated to be a suitable biomarker of effect for biomonitoring of workers handling AD due to its high sensitivity and non-invasivity.