title: Assessment of genotoxic risks in Croatian health care workers occupationally exposed to cytotoxic drugs: a multi-biomarker approach.
abstract: The aim of the present study was to evaluate genome damage induced in peripheral blood lymphocytes of Croatian health care workers occupationally exposed to cytotoxic drugs. A comprehensive multi-biomarker approach using the alkaline comet assay and cytogenetic endpoints (analysis of structural chromosome aberrations, SCE assay, lymphocyte proliferation kinetics and cytokinesis-block micronucleus assay) was employed. The study included two populations of subjects: 50 health care workers occupationally exposed to cytotoxic drugs and 50 control subjects matched in age, gender and smoking habit. An investigation regarding the handling practice with cytotoxic drugs was conducted in parallel. Results obtained indicate high exposure levels at workplace that should be reduced. The values recorded among the occupationally exposed subjects were as follows: mean comet tail length: 17.46+/-0.08 microm; the incidence of long-tailed nuclei: 54.68+/-3.93%; 4.48+/-0.33 structural chromosome aberrations per 200 cells; 5.81+/-0.04 SCE per 50 cells; 29.28+/-2.21% of high-frequency cells; proliferation rate index: 1.97+/-0.12; and 16.32+/-0.85 micronuclei per 1000 binuclear cells. All these values indicated higher levels of DNA and cytogenetic damage compared to the general population. Obtained results also confirmed that the frequency of long-tailed nuclei in the alkaline comet assay represents a helpful complement to other well-established comet parameters. The age of subjects and smoking habit significantly influenced the values of both comet and cytogenetic endpoints. Overall results of this study confirmed that handling cytotoxic drugs without appropriate safety precautions involves a potential genotoxic risk for exposed subjects. Before a strict monitoring of exposure levels on each workplace becomes a standard practice in Croatian hospitals, cytogenetic surveillance of exposed workers is also recommended, at least in cases of accidental exposure.
authors.affiliation: Mutagenesis Unit, Institute for Medical Research and Occupational Health, Ksaverska c. 2, HR-10 000 Zagreb, Croatia. nkopjar@imi.hr
authors.forename: Nevenka
authors.initials: N
authors.lastname: Kopjar
authors.forename: Verica
authors.initials: V
authors.lastname: Garaj-Vrhovac
authors.forename: Vilena
authors.initials: V
authors.lastname: Kasuba
authors.forename: Ruzica
authors.initials: R
authors.lastname: Rozgaj
authors.forename: Snjezana
authors.initials: S
authors.lastname: Ramić
authors.forename: Vesna
authors.initials: V
authors.lastname: Pavlica
authors.forename: Davor
authors.initials: D
authors.lastname: Zeljezić
mesh_terms: D000328:Adult; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood; D049109:Cell Proliferation / Q000187:drug effects; D002869:Chromosome Aberrations / Q000139:chemically induced*; D020552:Comet Assay / Q000379:methods; D017523:Croatia; D003582:Cytogenetics / Q000379:methods; D004249:DNA Damage / Q000187:drug effects; D004784:Environmental Monitoring / Q000379:methods*; D005260:Female; D005819:Genetic Markers; D006282:Health Personnel / Q000706:statistics & numerical data*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D048629:Micronuclei, Chromosome-Defective; D015162:Micronucleus Tests; D008875:Middle Aged; D009153:Mutagens / Q000633:toxicity*; D016273:Occupational Exposure / Q000009:adverse effects*; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D000395:Air Pollutants, Occupational; D000970:Antineoplastic Agents; D015415:Biomarkers; D005819:Genetic Markers; D009153:Mutagens