title: A study protocol for the evaluation of occupational mutagenic/carcinogenic risks in subjects exposed to antineoplastic drugs: a multicentric project.
abstract: BACKGROUND
  Some industrial hygiene studies have assessed occupational exposure to antineoplastic drugs; other epidemiological investigations have detected various toxicological effects in exposure groups labeled with the job title. In no research has the same population been studied both environmentally and epidemiologically. The protocol of the epidemiological study presented here uses an integrated environmental and biological monitoring approach. The aim is to assess in hospital nurses preparing and/or administering therapy to cancer patients the current level of occupational exposure to antineoplastic drugs, DNA and chromosome damage as cancer predictive effects, and the association between the two.
  
  
  METHODS
  About 80 healthy non-smoking female nurses, who job it is to prepare or handle antineoplastic drugs, and a reference group of about 80 healthy non-smoking female nurses not occupationally exposed to chemicals will be examined simultaneously in a cross-sectional study. All the workers will be recruited from five hospitals in northern and central Italy after their informed consent has been obtained.Evaluation of surface contamination and dermal exposure to antineoplastic drugs will be assessed by determining cyclophosphamide on selected surfaces (wipes) and on the exposed nurses' clothes (pads). The concentration of unmetabolized cyclophosphamide as a biomarker of internal dose will be measured in end-shift urine samples from exposed nurses. Biomarkers of effect and susceptibility will be assessed in exposed and unexposed nurses: urinary concentration of 8-hydroxy-2-deoxyguanosine; DNA damage detected using the single-cell microgel electrophoresis (comet) assay in peripheral white blood cells; micronuclei and chromosome aberrations in peripheral blood lymphocytes. Genetic polymorphisms for enzymes involved in metabolic detoxification (i.e. glutathione S-transferases) will also be analysed.Using standardized questionnaires, occupational exposure will be determined in exposed nurses only, whereas potential confounders (medicine consumption, lifestyle habits, diet and other non-occupational exposures) will be assessed in both groups of hospital workers.Statistical analysis will be performed to ascertain the association between occupational exposure to antineoplastic drugs and biomarkers of DNA and chromosome damage, after taking into account the effects of individual genetic susceptibility, and the presence of confounding exposures.
  
  
  CONCLUSIONS
  The findings of the study will be useful in updating prevention procedures for handling antineoplastic drugs.
authors: Department of Medical-Surgical Specialties and Public Health, University of Perugia, Via del Giochetto, 06122 Perugia, Italy.
authors: Massimo
authors: M
authors: Moretti
authors: Roberta
authors: R
authors: Bonfiglioli
authors: Donatella
authors: D
authors: Feretti
authors: Sofia
authors: S
authors: Pavanello
authors: Francesca
authors: F
authors: Mussi
authors: Maria G
authors: MG
authors: Grollino
authors: Milena
authors: M
authors: Villarini
authors: Anna
authors: A
authors: Barbieri
authors: Elisabetta
authors: E
authors: Ceretti
authors: Mariella
authors: M
authors: Carrieri
authors: Annamaria
authors: A
authors: Buschini
authors: Massimo
authors: M
authors: Appolloni
authors: Luca
authors: L
authors: Dominici
authors: Laura
authors: L
authors: Sabatini
authors: Umberto
authors: U
authors: Gelatti
authors: Giovanni B
authors: GB
authors: Bartolucci
authors: Paola
authors: P
authors: Poli
authors: Laura
authors: L
authors: Stronati
authors: Giuseppe
authors: G
authors: Mastrangelo
authors: Silvano
authors: S
authors: Monarca
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000970:Antineoplastic Agents / Q000633:toxicity*; D015415:Biomarkers / Q000652:urine; D002869:Chromosome Aberrations / Q000139:chemically induced*; D003430:Cross-Sectional Studies; D003520:Cyclophosphamide / Q000032:analysis; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004784:Environmental Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D007558:Italy; D009369:Neoplasms / Q000139:chemically induced*; D009741:Nursing Staff, Hospital; D009784:Occupational Diseases / Q000139:chemically induced*; D016273:Occupational Exposure / Q000032:analysis*; D009859:Oncology Nursing; D012306:Risk
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003520:Cyclophosphamide; D003849:Deoxyguanosine