title: Evaluation of genotoxic effects induced by exposure to antineoplastic drugs in lymphocytes and exfoliated buccal cells of oncology nurses and pharmacy employees.
abstract: The continuous introduction of new antineoplastic drugs and their use as complex mixture emphasize the need to carry out correct health risk assessment. The aim of this study was to evaluate genotoxic effects of antineoplastic drugs in nurses (n=25) and pharmacy technicians (n=5) employed in an oncology hospital. The nurses administered antineoplastic drugs in the day-care hospital (n=12) and in the wards (n=13), and pharmacy technicians prepared the drugs in the central pharmacy. We performed the micronucleus (MN) test with lymphocytes and exfoliated buccal cells and conducted traditional analysis of chromosomal aberrations (CA). Thirty healthy subjects were selected as controls. Monitoring of surface contamination with cyclophosphamide, 5-fluorouracil, ifosfamide, cytarabine, and gemcitabine showed the presence of detectable levels only for cyclophosphamide, 5-fluorouracil and ifosfamide. In addition, we measured the 5-fluorouracil metabolite alpha-F-betaalanine in the urine of all subjects and found significant concentrations only in 3 out of 25 nurses. The micronucleus assay with lymphocytes did not show significant differences between exposed and control groups, while the same test with exfoliated buccal cells found higher values in nurses administering antineoplastic drugs than in pharmacy employees. In the CA analysis, we detected in exposed groups a significant increase (about 2.5-fold) of structural CA, particularly breaks (up to 5.0-fold). Our results confirm the genotoxic effect of antineoplastic drugs in circulating blood lymphocytes. Moreover, in exfoliated buccal cells the data show more consistent genetic damage induced during administration of the antineoplastic drugs than during their preparation. The data also stress the use of this non-invasive sampling, to assess occupational exposure to mixture of chemicals at low doses.
authors.affiliation: Department of Occupational Medicine, ISPESL-National Institute for Occupational Safety and Prevention, Via Fontana Candida 1, 00040 Monteporzio Catone, Rome, Italy. delia.cavallo@ispel.it
authors.forename: Delia
authors.initials: D
authors.lastname: Cavallo
authors.forename: Cinzia Lucia
authors.initials: CL
authors.lastname: Ursini
authors.forename: Barbara
authors.initials: B
authors.lastname: Perniconi
authors.forename: Arianna Di
authors.initials: AD
authors.lastname: Francesco
authors.forename: Margherita
authors.initials: M
authors.lastname: Giglio
authors.forename: Federico Maria
authors.initials: FM
authors.lastname: Rubino
authors.forename: Alessandro
authors.initials: A
authors.lastname: Marinaccio
authors.forename: Sergio
authors.initials: S
authors.lastname: Iavicoli
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000633:toxicity*; D016022:Case-Control Studies; D002869:Chromosome Aberrations / Q000139:chemically induced*; D004249:DNA Damage; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008495:Medical Oncology; D015162:Micronucleus Tests; D008875:Middle Aged; D009061:Mouth Mucosa / Q000166:cytology / Q000187:drug effects; D009726:Nurses; D016273:Occupational Exposure; D010594:Pharmacies; D013048:Specimen Handling; D000078329:Workforce
chemical_list: D000970:Antineoplastic Agents