title: Occupational exposure to cytostatic/antineoplastic drugs and cytogenetic damage measured using the lymphocyte cytokinesis-block micronucleus assay: A systematic review of the literature and meta-analysis.
abstract: Many studies have reported the occurrence of work-environment contamination by antineoplastic drugs (ANPD), with significant incorporation of trace amounts of these hazardous drugs in hospital personnel. Given the ability of most ANPD to actively bind DNA, thus inducing genotoxic effects, it is of pivotal importance to assess the degree of genotoxic damage (i.e., residual genotoxic risk) in occupationally exposed subjects. The lymphocyte cytokinesis-block micronucleus (L-CBMN) assay is largely used for biological effect monitoring in subjects occupationally exposed to ANPD. In this study, we identified and analyzed the studies published reporting the use of the L-CBMN assay as biomarker of genotoxic risk in health care workers exposed to ANPD with the aim of performing meta-analysis and providing a meta-estimate of the genotoxic effect of exposure. We retrieved 24 studies, published from 1988 to 2015, measuring MN in peripheral blood lymphocytes in health care workers occupationally exposed to ANPD. In 15 out of the 24 studies (62.5%), increased MN frequencies were recognized in exposed subjects as compared to controls. The meta-analysis of MN frequency of the combined studies confirmed an association between occupational exposure to ANPD and cytogenetic effects with an overall meta-estimate of 1.67 [95% CI: 1.41-1.98]. In 16 out of the 24 studies (66.6%) at least one other genotoxicity biomarker, besides L-CBMN assay, was employed for biological effect monitoring. In several studies the effect of exposure to ANPD was evaluated also in terms of MN in exfoliated buccal cells. Other studies focused on genotoxicity endpoints, such as sister chromatid exchanges (3 studies), chromosome aberrations (6 studies), or primary DNA damage investigated by comet assay (7 studies). Overall, there was good agreement between other genotoxicity tests employed and L-CBMN assay outcomes.
authors.affiliation: Department of Pharmaceutical Sciences, (Unit of Public Health), University of Perugia, Via del Giochetto, 06122 Perugia, Italy. Electronic address: milena.villarini@unipg.it.
authors.forename: M
authors.initials: M
authors.lastname: Villarini
authors.affiliation: Department of Pharmaceutical Sciences, (Unit of Public Health), University of Perugia, Via del Giochetto, 06122 Perugia, Italy; Department of Experimental Medicine (School of Specialization in Hygiene and Preventive Medicine), University of Perugia, Piazzale Gambuli, 06132 Perugia, Italy. Electronic address: vincenza.gianfredi@studenti.unipg.it.
authors.forename: V
authors.initials: V
authors.lastname: Gianfredi
authors.affiliation: Department of Pharmaceutical Sciences, (Unit of Public Health), University of Perugia, Via del Giochetto, 06122 Perugia, Italy. Electronic address: sara.levorato@unipg.it.
authors.forename: S
authors.initials: S
authors.lastname: Levorato
authors.affiliation: Department of Pharmaceutical Sciences, (Unit of Public Health), University of Perugia, Via del Giochetto, 06122 Perugia, Italy. Electronic address: samuele.vannini@unipg.it.
authors.forename: S
authors.initials: S
authors.lastname: Vannini
authors.affiliation: Department of Pharmaceutical Sciences, (Unit of Public Health), University of Perugia, Via del Giochetto, 06122 Perugia, Italy. Electronic address: tania.salvatori@unipg.it.
authors.forename: T
authors.initials: T
authors.lastname: Salvatori
authors.affiliation: Department of Pharmaceutical Sciences, (Unit of Public Health), University of Perugia, Via del Giochetto, 06122 Perugia, Italy. Electronic address: massimo.moretti@unipg.it.
authors.forename: M
authors.initials: M
authors.lastname: Moretti
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D048749:Cytokinesis / Q000187:drug effects*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000648:ultrastructure; D015162:Micronucleus Tests / Q000379:methods*; D016273:Occupational Exposure
chemical_list: D000970:Antineoplastic Agents
keywords: Antineoplastic drugs; Cytokinesis-block micronucleus assay; Meta-analysis; Occupational exposure