Assessment of primary, oxidative and excision repaired DNA damage in hospital personnel handling antineoplastic drugs

Abstract

The International Agency for Research on Cancer has classified several antineoplastic drugs in Group 1 (human carcinogens), among which chlorambucil, cyclophosphamide (CP) and tamoxifen, Group 2A (probable human carcinogens), among which cisplatin, etoposide, N-ethyl- and N-methyl-N-nitrosourea, and Group 2B (possible human carcinogens), among which bleomycins, merphalan and mitomycin C. The widespread use of these mutagenic/carcinogenic drugs in the treatment of cancer has led to anxiety about possible genotoxic hazards to medical personnel handling these drugs. The aim of the present study was to evaluate work environment contamination by antineoplastic drugs in a hospital in Central Italy and to assess the genotoxic risks associated with antineoplastic drug handling. The study group comprised 52 exposed subjects and 52 controls. Environmental contamination was assessed by taking wipe samples from different surfaces in preparation and administration rooms and nonwoven swabs were used as pads for the surrogate evaluation of dermal exposure, 5-fluorouracil and cytarabine were chosen as markers of exposure to antineoplastic drugs in the working environment. The actual exposure to antineoplastic drugs was evaluated by determining the urinary excretion of CP. The extent of primary, oxidative and excision repaired DNA damage was measured in peripheral blood leukocytes with the alkaline comet assay. To evaluate the role, if any, of genetic variants in the extent of genotoxic effects related to antineoplastic drug occupational exposure, the study subjects were genotyped for GSTM1, GSTT1, GSTP1 and TP53 polymorphisms. Primary DNA damage significantly increased in leukocytes of exposed nurses compared to controls. The use of personal protective equipment (i.e. gloves and/mask) was associated with a decrease in the extent of primary DNA damage.

Biological Effect Monitoring in Peripheral Blood Lymphocytes from Subjects Occupationally Exposed to Antineoplastic Drugs: Assessment of Micronuclei Frequency

“…In this paper, we report the results of a biological effect monitoring study performed to complete the assessment of genetic effects of exposure to environmental genotoxins in a group of health-care workers occupationally exposed to ANPDs. The frequency of MNs was evaluated in PBLs of subjects also monitored for primary DNA damage by the comet assay 23) . The alkaline comet assay detects primary DNA lesions (e.g., DNA double-and single-strand breaks, alkali-labile sites such as apurinic/apyrimidinic sites and incomplete excision repair sites) present in leukocytes (or lymphocytes) at the time of blood sampling 29) .…”

“…The results indicated no exposure-related excess of MNs in exposed subjects compared with controls, despite the occurrence of detectable environmental Table 4. Frequency of MNs per 1,000 binucleated lymphocytes and CBPI in nurses exposed to antineoplastic drugs and nonexposed subjects with respect of gender, age and smoking habits (whole population) and occupational assignment, job seniority and personal protection (exposed subjects) contamination by 5-fluorouracil (5FU) and cytarabine (CYT) on selected surfaces (wipes) and on the exposed nurses' clothes (pads) 23) . Similar to our findings, negative results for MN induction were reported in other investigations on workers exposed to ANPDs 11−15) .…”

“…Similar to our findings, negative results for MN induction were reported in other investigations on workers exposed to ANPDs 11−15) . As reported previously 23) , healthcare workers handling ANPDs were evaluated for genotoxic damage in peripheral blood leukocytes, and primary DNA damage was evaluated by applying the comet assay for detecting early biological effects of DNA-damaging agents (i.e., antineoplastic drugs). We found higher DNA migration extents in the exposed subjects when compared with the controls.…”

“…In a previously published paper 23) , we reported the results of DNA damage (assessed by the alkaline comet assay) in peripheral blood leukocytes of workers handling ANPDs; the levels of environmental exposure were evaluated by the wipe test and the degree of skin exposure by pads; the determination of urinary cyclophosphamide was also used as an indicator of biological uptake of specific ANPDs. On average, analysis of contamination in the work environment showed the presence of trace amounts of ANPDs, and urine samples were positive for cyclophosphamide in about 13% of the workers.…”

Antineoplásicos e os riscos ocupacionais para os enfermeiros: uma revisão integrativa

“…Siendo los daños a los enfermeros mayores y más significativos que los causados a los farmacéuticos [5][6][7] .…”