Evaluation of early DNA damage in healthcare workers handling antineoplastic drugs.
OBJECTIVE
This study evaluates by comet assay the induction of early DNA damage in healthcare workers of an oncology hospital regularly handling antineoplastic drug mixtures. The aim was to identify a suitable biomarker of DNA damage by exposure to low levels of such drugs.


METHODS
We studied 12 day hospital nurses and 13 oncology ward nurses who performed up to 300 and up to 35 drug administrations per week, respectively, and five pharmacy employees who regularly prepared mixtures of antineoplastic agents. Thirty healthy subjects were selected as controls. For exposure evaluation, we performed environmental monitoring of 5-fluorouracil, cytarabine, gemcitabine, cyclophosphamide, and ifosfamide in selected work areas of pharmacy and day hospital units and biological monitoring of urine for the 5-fluorouracile metabolite, alpha-fluoro-beta-alanine. We evaluated early DNA damage in lymphocytes and exfoliated buccal cells by comet assay measuring tail moment (TM) parameter that indirectly indicates the presence of DNA damage.


RESULTS
Environmental monitoring detected cyclophosphamide, 5-fluorouracil and ifosfamide, with higher levels of contamination in day hospital unit. The biological monitoring measured detectable levels of alpha-fluoro-beta-alanine only in three nurses. Comet assay showed an increase on exfoliated buccal cells, even if not statistically significant, of mean TM with respect to controls in day hospital nurses (43.2 vs. 28.6, respectively) while ward nurses and pharmacy technicians did not show differences. Comet assay performed on lymphocytes did not show appreciable differences between exposed and controls.


CONCLUSIONS
The employment of the sensitive comet assay, which is able to detect early the effects of a recent exposure to genotoxic substances, allowed us to find a slight DNA damage, only on exfoliated buccal cells of day hospital nurses, the group handling the highest amount of drugs during the administration process. This finding suggests that comet assay on exfoliated buccal cells could represent a useful tool to evaluate early and still repairable genotoxic effects of exposure to antineoplastic drug mixtures and then contribute to the improvement of the hospital safety practices.
Ursini
Cinzia Lucia
CL
Dipartimento Medicina del Lavoro ISPESL, Via Fontana Candida 1, 00040, Monteporzio Catone (Roma), Italy. c.lucia.ursini@tin.it
Cavallo
Delia
D
Colombi
Antonio
A
Giglio
Margherita
M
Marinaccio
Alessandro
A
Iavicoli
Sergio
S
D000328:Adult; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000032:analysis* / Q000633:toxicity; D015415:Biomarkers; D002173:Cancer Care Facilities; D020552:Comet Assay; D003520:Cyclophosphamide / Q000032:analysis / Q000633:toxicity; D003561:Cytarabine / Q000032:analysis / Q000633:toxicity; D004249:DNA Damage; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000032:analysis / Q000633:toxicity; D004784:Environmental Monitoring / Q000379:methods*; D062665:Epidemiological Monitoring; D005260:Female; D005472:Fluorouracil / Q000032:analysis / Q000633:toxicity; D006801:Humans; D007069:Ifosfamide / Q000032:analysis / Q000633:toxicity; D007558:Italy / Q000453:epidemiology; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000187:drug effects; D009741:Nursing Staff, Hospital / Q000145:classification* / Q000706:statistics & numerical data; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis*; D010607:Pharmacy Service, Hospital; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D015415:Biomarkers; D003561:Cytarabine; D003841:Deoxycytidine; D003520:Cyclophosphamide; D005472:Fluorouracil; D007069:Ifosfamide; D000093542:Gemcitabine