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Iranian J. Publ. Health, Vol. 30, Nos. 1-2, PP. 37-40, 2001
Iranian J. Publ. Health, Vol. 30, Nos. 1-2, PP. 37-40, 2001
Sister Chromatid Exchanges and Micronuclei in Lymphocyte of
Nurses Handling Antineoplastic Drugs
∗M Ansari-Lari1, M Saadat2, M Shahryari3, DD Farhud4
1Dept. of Social Medicine school of Medicine, Shiraz University of Medical Sciences, Iran. 2Dept. of Biology, College of Sciences, Shiraz University, Iran. 3Dept. of Pediatric, School of Medicine, Shiraz University of Medical Sciences, Iran. 4Dept. of Human Genetics, School of Public Health, Tehran University of Medical Sciences, P.O.Box 14155-6446, Tehran, Iran.
Key Words: Antineoplastic drugs, sister chromatid exchange, micronuclei, occupational exposure
ABSTRACT
Individuals handling antineoplastic drugs or their wastes may absorb these potent genotoxic agents. The effects of handling antineoplastic drugs were
examined in a group of 24 nurses working in the hematology and oncology departments of two different university hospitals in Shiraz (Iran) and in a
group of 18 unexposed nurses as control group. The cytogenetic repercussions of exposure were assessed by examining sister chromatid exchanges
(SCEs) and micronuclei (Mn) in circulating lymphocytes. A significant increased frequencies of SCE and Mn is observed in circulating lymphocytes.
A significant increased frequencies of SCE and Mn is observed in nurses in daily contact with antineoplastic drugs as compared to control group.
INTRODUCTION
Anticancer drugs target cancers because cell division is rapid in
Thus, to detect mutagenic effects of antineoplastic drugs on cancerous tissue. These drugs affect other proliferating non- occupational exposure, SCEs, and Mn were analysed in hospital cancerous tissues such as bone marrow, hair follicles, nurses regularly handling such drugs and in non-exposed gastrointestinal, nasopharyngeal and genitourinary tract controls. epithelia, and developing embryos. The antineoplastic drugs are known to be carcinogens and teratogens in experimental MATERIALS AND METHODS
animals (28). Several anticancer chemotherapeutic agents have Subjects
cytogenetic effects and induce mutations in bacteria and Twenty-four healthy female nurses, in the age range 22 to 43 cultured mammalian cells (28). It is shown that at least some years, were studies. These nurses had been handling cancer chemotherapeutic drugs, particularly alkylating agents, antineoplastic drugs for a range of 1-10 years. Blood samples cause second malignancies, most commonly leukemias, were obtained from hospital nurses exposed to antineoplastic lymphomas, and sarcomas (7). drugs in oncology and hematology sections at 2 different It has aberrations, the majority of which are balanced hospitals of Shiraz, Iran (Nemazi hospital and Ali-Asgar rearrangements, persist for many years in children who have hospital). We have also studied unexposed nurses, as controls survived for extended periods after chemotherapy of cancer from those hospitals. There was no statistically significant age (18). Increased frequencies of chromosomal aberrations sister difference between the oncology/hematology nurses (age range = chromatid exchanges (SCE) (6, 11, 12, 17, 20, 22, 25), and 22 to 43 years; average age = 28.5 years) and the control group micronuclei (Mn) (3,10) have been reported in peripheral (age range = 21 to 41 years; average age = 29.1years). lymphocytes of cancer patients been receiving chemotherapy. The most frequently handled drugs included Cylophosphamide, Scientific articles regarding potential or actual hazards of Methotrexate, Vincristine, Adriamycin, Cisplatinum, Etoposide, cytotoxic drug exposure have been appearing in medical, 5-Fluorouracil and Bleomycin. Eighteen unexposed healthy pharmaceutical, and nursing literature for many years (1-4). female nurses ranging in age from 21 to 41 years served as Direct exposure to cytotoxic agents can occur during controls. admixture, administration, or handling and involve inhalation, In order to identify any of the factors that may confound the analysis of SCEs, and micronuclei test, two groups were asked to Setting where many of these drugs are administered or prepared fill in a questionnaire about their extraoccupational exposure such (hospitals, home health agencies, pharmacies, waste handlers, as smoking, drug consumption, viral diseases, dietary habits and and outpatient settings) need sensitive,selective, non invasive, other factors which potentially play a role in the induction or and in expensive screening tests reflecting absorption of many expression and/or alteration of SCE, and Mn. Analysis of SCE (13, 23, 32) and Mn test (5, 15, 16, 26) are Sister Chromatid Exchange (SCE) Analysis
sensitive means of detecting DNA damage in proliferating cells For the SCE analysis, standard cultures with 0.4 ml whole blood, and the tests have also been used for monitoring human 8 ml RPMI-1640 medium, 15% heat-inactivated fetal calf serum populations for exposure to environmental mutagens. The 0.2 ml, PHA-M and 3mg/ml 5-bromodeoxy uridine (BrdU) were effects of handling antineoplastic drugs on SCEs in used. The Cultures were incubated in complete darkness at 37°C lymphocytes in vivo is still being discussed. Some studies for 72 h, and Colchicine (0.9 mg/ml) was present in the cultures report an increase in SCE frequencies (1, 19, 21, 30, 31) while for the final 1.5 h. The cells were harvested by exposure to others do not confirm these observations (2, 4, 8, 24,27, 29). Corresponding author, Tel:+ 98 -711-2282747; Fax: + 98-711-2280926; E-mail: ansarim47@yahoo.com Corresponding author, Tel:+ 98 -711-2282747; Fax: + 98-711-2280926; E-mail: ansarim47@yahoo.com Ansari-Lari, et al.; Sister Chromatid Exchanges …
hypotonic solution with 0.075 M KCl for 20 min at 37°C, b) During adminstration: Syringes leak during transport, and fixed in methanol and acetic acid (3:1). Slides were priming of intravenous sets, expelling of air, and prepared and stained using the Giemsa technique (9). SCEs connection to or removal from the patient. Aerosols form were analyzed in 30 cells containing 46 chromosomes in during priming, expelling of air, and connection to or each preparation, and the mean SCE frequency was calculated as SCEs, per cell of each subject. c) Miscellaneous exposures: Discarded containers contaminate housekeeping workers. Also, improperly Micronuclei Test
cleaned equipment/containers and patient excreta are In order to study the Mn, the blood smear were prepared and the slides were stained using 5% SCE Analysis
A statistically significant difference in the number of SCE Statistical Analysis
was observed between the exposed and control goups The significance of differences was assessed using (Table 1). The mean frequency of SCE/cells was 7.12 ± unpaired Student's t-test and proportional Z-test. A 0.80 and 5.81 ± 1.20 in the oncology/hematology and probability of P<0.05 considered statistically control group nurses, respectively. Which shows significant difference between the studied groups (t = 4.32; df = 40; Observations
Micronucleus Test
Direct observation revealed the following potential The results of micronuclei determination are indicated in a) During preparation: powder particles and liquid droplets Table 2. The frequency of micronuclei amoung aerosolize. Also, spills, leaks, and container/syringe oncology/hematology nurses, was significantly higher (Z- breakage occure during transport from or to the pharmacy value =3.65) as compared to those of the control group. Table1. Frequency of SCE in blood lymphocytes among oncology/hematology nurses and control nurses
SCE/cell*
Oncology/hematology
Table 2. Micronuclei in peripheral blood lymphocytes (micronuclei/1000 cells)
in oncology/hematology nurses and control nurses
Mn/1000 cells
Oncology/hematology
DISCUSSION
Biological monitoring with SCE, chromosomal aberration, and This study is the first to report the effect of handling anticancer forward mutation assays has also produced positive results in drugs on oncology nurses in Iran. The results of the present nurses (1, 19, 21, 27, 28, 30, 31); however, several studies study shows that among nurses working in hematology and could not demonstrate any relationship between occupational oncology departments, those handling antineoplastic drugs exposure to cytostatic drugs and increased SCEs or other exhibited a significant increases in the number of SCEs and system assays (2, 4,8, 24, 29). We assume that different results may occur from the low levels and average duration of exposure and that some of the nurses may have been using protective measures while handling these drugs; i.e.wearing Iranian J. Publ. Health, Vol. 30, Nos. 1-2, PP. 37-40, 2001
surgical masks, gloves, and using vertical laminar flow hoods Korenberg JR and Freedlender EF (1974): Giemsa technique for the detection of sister chromatid exchanges. Biomonitoring of occupationally exposed people appears to be Chromosoma, 48: 355-60.
a sensitive way to evaluate the genotoxic effects of cytostatic 10. Krogh-Jensen M and Nyfors A (1979): Cytogenetic of drugs exposures (and radiation exposures). This type of methotrexate on human cells in vivo, comparison between monitoring may be used as an indicator to detect early damage results obtained by chromosome studies on bone-marrow cells and blood lymphocytes and by the micronucleus test. The purpose of this work was to provide data on the genetic Mutat Res, 64: 339.
hazards due to the occupational exposure to antineoplastic 11. Lambert B, Ringborg V, Harper E and Lindblad A (1978): drugs. Since the potential risks and biological consequences of Sister chromatid exchange in lymphocyte culture of anticancer drugs have been attained through the extrapolation patients. Cancer Treat Rep, 62: 1413-9.
12. Lambert B, Ringborg U and Lindblad A (1979): Prolonged Our results are also particularly interesting for a developing increase of sister chomatid exchanges in lymphocytes of country such as ours, where biological security controls are not melanoma patients after CCNU treatment. Mutat Res, 59:
so strict and extended work days are common. For health 13. Latt SA and Schrik RR (1980): Sister chromatid exchange surveillance, the detection of early genotoxic effects may analysis. Hum Genet, 32: 297-313.
permit the adoption of preventive biological controls such as 14. Ledebur von M and Schmid W (1973): The micronucleus hygienic improvements in the workplace or the reduction of test. Methodological aspects. Mutat Res, 19: 109.
15. Matter BE and Schmid W (1971): Trenimon - induced chromosomal damage in bone marrow cells of six ACKNOWLEDGEMENT
mammalian species, evaluated by the micronucleus test. Mutat Res, 12: 417.
This study was supported by the Shiraz University, project No. 16. Migliore L, Parrini M and Sbrana I (1991): Micronucleated 76-Sc-980-587. Thanks are due Mrs. B. Shams, and Mr. B. lymphocytes in people occupationally exposed to potential Faramarzi for their skillful assistance. evironmental contaminants: the age effect. Mutat Res, 256:
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Iranian J. Publ. Health, Vol. 30, Nos. 1-4, PP. 35-34, 2001

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