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Micronuclei and chromosome aberrations in subjects occupationally exposed to antineoplastic drugs: a multicentric approach

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Abstract

Objectives

Recently published works showed that occupational exposure to antineoplastic drugs (ANPD) is still frequent in hospital settings, despite significant safety policy improvements. The aim of this study was to assess the current level of occupational exposure to ANPD and any potentially associated cytogenetic damages in hospital nurses routinely handling ANPD.

Methods

Occupationally ANPD-exposed (n = 71) and ANPD-unexposed (n = 77; control) nurses were recruited on a voluntary basis from five hospitals in Northern and Central Italy. Evaluation of surface contamination and dermal exposure to ANPD was assessed by determining cyclophosphamide (CP) on selected surfaces (wipes) and on exposed nurses’ clothes (pads). The concentration of unmetabolized CP—as a biomarker of internal dose—was measured in end-shift urine samples. Biomonitoring of genotoxic effects (i.e., biological effect monitoring) was conducted by analyzing micronuclei (MN) and chromosome aberrations (CA) in peripheral blood lymphocytes. Genetic polymorphisms for enzymes involved in metabolic detoxification (i.e., glutathione S-transferases) were analyzed as well.

Results

We observed a significant increase in MN frequency (5.30 ± 2.99 and 3.29 ± 1.97; mean values ± standard deviation; p < 0.0001) in exposed nurses versus controls, as well as in CA detection (3.30 ± 2.05 and 1.84 ± 1.67; p < 0.0001), exposed subjects versus controls. Our results provide evidence that, despite safety controlled conditions, ANPD handling still represents a considerable genotoxic risk for occupationally exposed personnel.

Conclusions

Because both MN and CA have been described as being predictive of group-increased cancer risk, our findings point to a need for improving specific safety procedures in handling and administering ANPD.

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Acknowledgments

The authors wish to thank the nurses for participating in the study as exposed subjects or controls. We are grateful to Prof. Paolo Puccetti, Department of Experimental Medicine, University of Perugia, for reading the manuscript and offering constructive comments. The study was funded by the Italian Ministry of Education, University and Scientific Research (MIUR), Research No. 2005-062547.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Perugia, Via del Giochetto, 06122, Perugia, Italy

    Massimo Moretti, Milena Villarini, Luca Dominici, Cristina Fatigoni & Silvano Monarca

  2. Unit of Radiation Biology and Human Health, ENEA CR Casaccia, Via Anguillarese 301, 00123, Rome, Italy

    Maria Giuseppa Grollino, Massimo Appolloni & Laura Stronati

  3. Department of Cardiological, Thoracic and Vascular Sciences, University of Padova, Via Giustiniani 2, 35128, Padua, Italy

    Sofia Pavanello, Mariella Carrieri, Giuseppe Mastrangelo & Giovanni Battista Bartolucci

  4. Department of Medical and Surgical Sciences, Sant’Orsola-Malpighi Hospital, University of Bologna, Via Palagi 9, 40138, Bologna, Italy

    Roberta Bonfiglioli, Laura Sabatini & Anna Barbieri

  5. Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Viale Europa 11, 25123, Brescia, Italy

    Elisabetta Ceretti

  6. Department of Genetics, Biology of Microorganisms, Anthropology, Evolution, University of Parma, Parco Area delle Scienze 11A, 43124, Parma, Italy

    Francesca Mussi

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  1. Massimo Moretti
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Moretti, M., Grollino, M.G., Pavanello, S. et al. Micronuclei and chromosome aberrations in subjects occupationally exposed to antineoplastic drugs: a multicentric approach. Int Arch Occup Environ Health 88, 683–695 (2015). https://doi.org/10.1007/s00420-014-0993-y

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