Evaluation of genotoxic effects induced by exposure to antineoplastic drugs in lymphocytes and exfoliated buccal cells of oncology nurses and pharmacy employees.

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.

[1]  P. Sessink,et al.  Environmental contamination and assessment of exposure to antineoplastic agents by determination of cyclophosphamide in urine of exposed pharmacy technicians: is skin absorption an important exposure route? , 1994, Archives of environmental health.

[2]  G. Zúñiga-González,et al.  Evaluation of cisplatin + 5-FU, carboplatin + 5-FU, and ifosfamide + epirubicine regimens using the micronuclei test and nuclear abnormalities in the buccal mucosa. , 2003, Mutation research.

[3]  A. Pietropaolo,et al.  Measurement of surface contamination from nucleoside analogue antineoplastic drugs by high-performance liquid chromatography in occupational hygiene studies of oncologic hospital departments. , 1999, Journal of chromatography. B, Biomedical sciences and applications.

[4]  D. Anderson,et al.  Monitoring of occupational exposure to cytostatic anticancer agents. , 1996, Mutation research.

[5]  W. Vollmer,et al.  Antineoplastic drug handling protection after OSHA guidelines. Comparison by profession, handling activity, and work site. , 1992, Journal of occupational medicine. : official publication of the Industrial Medical Association.

[6]  R. P. Bos,et al.  Exposure of Pharmacy Technicians to Antineoplastic Agents: Reevaluation after Additional Protective Measures , 1997 .

[7]  G. Fruhmann,et al.  Biological monitoring of cyclophosphamide and ifosfamide in urine of hospital personnel occupationally exposed to cytostatic drugs. , 1994, Occupational and environmental medicine.

[8]  P J Baxter,et al.  Occupational exposure to cytotoxic drugs in two UK oncology wards , 2002, Occupational and environmental medicine.

[9]  L. Tyler,et al.  Using a closed-system protective device to reduce personnel exposure to antineoplastic agents. , 2003, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[10]  D. M. Roth,et al.  Occupational genotoxicity risk evaluation through the comet assay and the micronucleus test. , 2003, Genetics and molecular research : GMR.

[11]  R. Anzion,et al.  Urinary cyclophosphamide excretion and micronuclei frequencies in peripheral lymphocytes and in exfoliated buccal epithelial cells of nurses handling antineoplastics. , 1999, Mutation research.

[12]  J. Yager,et al.  Biological and environmental monitoring of occupational exposure to cyclophosphamide in industry and hospitals. , 1988, Mutation research.

[13]  M. Rosin.  The use of the micronucleus test on exfoliated cells to identify anti-clastogenic action in humans: a biological marker for the efficacy of chemopreventive agents. , 1992, Mutation research.

[14]  F. Sarto,et al.  Chromosomal aberrations, sister chromatid exchanges, and urinary thioethers in nurses handling antineoplastic drugs. , 1990, American journal of industrial medicine.

[15]  H. Stich,et al.  ADAPTATION OF THE DNA‐REPAIR AND MICRONUCLEUS TESTS TO HUMAN CELL SUSPENSIONS AND EXFOLIATED CELLS * , 1983, Annals of the New York Academy of Sciences.

[16]  A. Fucic,et al.  Cytogenetic consequences after occupational exposure to antineoplastic drugs. , 1998, Mutation research.

[17]  P. Sessink,et al.  Surface contamination with antineoplastic agents in six cancer treatment centers in Canada and the United States. , 1999, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[18]  R. Anzion,et al.  Assessment of genotoxic damage in nurses occupationally exposed to antineoplastics by the analysis of chromosomal aberrations , 2002, Human & experimental toxicology.

[19]  J. Śanchez-Corona,et al.  Determination of diesel genotoxicity in firebreathers by micronuclei and nuclear abnormalities in buccal mucosa. , 1998, Mutation research.

[20]  P. Tolbert,et al.  Micronuclei and other nuclear anomalies in buccal smears: methods development. , 1992, Mutation research.

[21]  R. Schierl,et al.  Biological monitoring of hospital pharmacy personnel occupationally exposed to cytostatic drugs: urinary excretion and cytogenetics studies , 1997, International archives of occupational and environmental health.

[22]  P. Sessink,et al.  Assessment of occupational exposure of pharmaceutical plant workers to 5-fluorouracil. Determination of alpha-fluoro-beta-alanine in urine. , 1994, Journal of occupational medicine. : official publication of the Industrial Medical Association.

[23]  Dennis Nowak,et al.  Uptake of antineoplastic agents in pharmacy and hospital personnel. Part I: monitoring of urinary concentrations , 2003, International archives of occupational and environmental health.

[24]  S. Maluf,et al.  Follow-up study of the genetic damage in lymphocytes of pharmacists and nurses handling antineoplastic drugs evaluated by cytokinesis-block micronuclei analysis and single cell gel electrophoresis assay. , 2000, Mutation research.

[25]  P. Apostoli,et al.  Application of high performance liquid chromatography/tandem mass spectrometry in the environmental and biological monitoring of health care personnel occupationally exposed to cyclophosphamide and ifosfamide. , 1998, Rapid communications in mass spectrometry : RCM.

[26]  P. Sessink,et al.  Detection of contamination with antineoplastic agents in a hospital pharmacy department , 1992, Pharmaceutisch Weekblad.

[27]  Dianne M. Bennett,et al.  OSHA work-practice guidelines for personnel dealing with cytotoxic (antineoplastic) drugs. Occupational Safety and Health Administration. , 1986, American journal of hospital pharmacy.

[28]  H. Stettner,et al.  Long-term monitoring of sister chromatid exchanges and micronucleus frequencies in pharmacy personnel occupationally exposed to cytostatic drugs , 2000, International archives of occupational and environmental health.

[29]  R. Jacob,et al.  Micronuclei in lymphocytes and exfoliated buccal cells of postmenopausal women with dietary changes in folate. , 1997, Mutation research.

[30]  A. Sartorelli,et al.  Antineoplastic and Immunosuppressive Agents , 1975, Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology.

[31]  M. Fenech,et al.  Measurement of micronuclei in lymphocytes. , 1985, Mutation research.

[32]  A. Pietropaolo,et al.  Measurement of surface contamination by certain antineoplastic drugs using high-performance liquid chromatography: applications in occupational hygiene investigations in hospital environments. , 1999, La Medicina del lavoro.

[33]  G. Fruhmann,et al.  The genotoxic risk of hospital, pharmacy and medical personnel occupationally exposed to cytostatic drugs--evaluation by the micronucleus assay. , 2001, Mutation research.

[34]  F. Kassie,et al.  Use of the micronucleus assay with exfoliated epithelial cells as a biomarker for monitoring individuals at elevated risk of genetic damage and in chemoprevention trials. , 2001, Mutation research.