Mat&on Research, 27Y (1992) 117-120 0 1992 Elsevier Science Publishers B.V. All rights reserved 01651218/92/$05.00

117

MUTGEN 01757

Sister-chromatid

exchanges in operating room personnel

S. !$ardag, H. Cuhruk, A.E. Karakaya and Y. Atakurt UniLlersityof Gazi, Department of Toxicology, Faculty of Pharmacy, Ankara, Universityof Ankara, Department of Anaesthesia. Faculty of Medicine, Ankara and Department of Statistics,Far& of Medicine, Ankara (Turkey)

(Received 16 June 1991) (Revision received 10 October 1991) (Accepted 29 October 1991)

Keywor& Sister-chromatid exchanges; Anaesthetic gases

Summary Sister-chromatid exchange (SCE) analysis was carried out in 67 operating room personnel (anaesthetists M.D.; anaesthesia nurses and anaesthesia unit technicians) exposed to waste anaesthetic gases such as halothane, nitrous oxide and isoflurane and in 50 healthy unexposed controls. The SCE frequencies were increased significantly in operating room personnel as compared to controls. A significant increase in SCEs was found in non-smoking operating room personnel as compared to non-smoking controls. This study supports the existence of an association between occupational exposure to mutagens and an increase in SCEs in lymphocytes.

The possibility of a potential mutagenic/ carcinogenic action of inhalation anaesthetics has been the subject of various studies (Baden et al., 1977, 1978; Waskell, 1978; White et al., 1979; Baden and Simmon, 1980). Although experimental and epidemiological studies have indicated indirectly that working in an environment contaminated by waste anaesthetic gases may be a health hazard (Spence and Grill-Jones, 1978; Vessey and Nunn, 1980) a causal relationship has never been established (Husum et al., 1982). Among cytogenetic tests the sister-chromatid exchange (SCE) test is considered to be a sensitive

Correspondence: Dr. Semra .$arda$, Gazi University, Faculty of Pharmacy, Department of Toxicology, 06330 Ankara (Turkey).

end point for evaluating the genotoxic potential of mutagenic and carcinogenic agents. Although the molecular mechanism leading to SCE formation is not understood, SCE are believed to reflect damage of DNA. SCE in anaesthetized patients have been investigated by Husum et al., with no elevation of SCE frequencies found after short-term exposure to fluroxene, halothane and isoflurane (Husum et al., 1982, 1984, 1985a), or after occupational exposure to these compounds (Husum and Wulf, 1980; Husum et al., 1983, 1985b, 1986). However, the duration of employment in those studies was shorter than in the present report. We therefore performed a study of 67 operating room personnel currently employed at the Ankara University Department of Anaesthesia, who had been continuously exposed to various anaesthetics (halothane, nitrous oxide and isoflurane) for 2-29 years.

posure to other potential hazards such as smoking, drug consumption, viral diseases, recent vaccinations and radiodiagnostic examinations.

Materials and methods

We analyzed 67 occupationally exposed persons and 50 controls. The exposed group comprised 18 anaesthetists M.D., 20 anaesthesia nurses and 29 anaesthesia unit technicians who agreed to participate in the study. All were in general good health and none were taking regular medication, except two nurses who used oral contraceptives. All subjects were asked to fill in a detailed questionnaire including items concerning their occupational exposure. Subjects were also asked to state whether they had previously worked in radiotherapy or radiodiagnostic wards, in laboratories, or in units responsible for disinfection and sterilization, since all these occupations are suspected of involving mutagenic hazards. The questionnaires also included items concerning ex-

Sister-chromatid exchange (SCE) Peripheral blood samples were taken from each subject and placed in culture on the same day. The culture medium contained TC 199 Medium (Gibco Grand Island, NY, U.S.A.) supplemented with 20% fetal calf serum (Gibco), 100 U penicillin/ml, 100 pg streptomycin/ml (Gibco), 0.25 ml phytohaemagghrtinin (Sigma, St. Louis, MO, U.S.A.) and 10 pg/ml 5bromodeoxyuridine (Sigma). The cultures were incubated in the dark at 37°C for 72 h. During the last 3 h of incubation 0.5 pg/ml colchicine (Gibco) was added to the culture. Preparations were made following a routine protocol and stained differentially according

TABLE I MEAN NUMBER OF SCEs IN LYMPHOCYTES OF EXPOSED SUBJECTS AS A FUNCTION OF SMOKING STATUS Mean SCE/cell+

Smokers Non-smokers All subjects

OPERATING

ROOM PERSONNEL

AND CONTROL

P value

SD

Exposed

Controls

X.o6+2.0s(n = 33) h.98+ 1.7Oln = 34) 7.66f 1.81 (n = 67)

h.S2f 1.47(n = 23) 4.1 I fO.Y4(n = 27) 5.22+ 1.70(n = 50)

p < 0.01 p < 0.001 p c 0.001

II. number of subjects.

TABLE 2 SCEs IN 67 OPERATING ROOM PERSONNEL IN RELATION TO ANAESTHETIC GASES AND SMOKING HABITS Group Anaesthetists M.D. Non-smokers Smokers Anaesthesia unit technicians Non-smokers Smokers Anaesthesia nurses Non-smokers Smokers

No. IX 9 9 29 IS 14 20 IO II)

TO AGE, OCCUPATION,

DURATION

OF EXPOSURE

Age (years) mean _ISD

Occupational exposure (years)

Mean SCE/cell+

32.33 + 6.84 33.33 + 6.73 31.33+ 7.21 40.14+5.52 41.47k4.96 38.71 k5.92 24.25 + 3.48 24.00 + 2.95 24.00 +4.0X

7.17k7.46 K.00 f 7.69 6.33 f 7.59 11.10+7.02 Il.87f8.14 10.29+ 5.77 4.65 f 2.35 4.40 + 2.55 4.90+ 2.23

7.h7 f 2.00 6.89 + 1.K3 8.44 + 1.94 8.28k 1.77 * 7.93 * 1.28 * 8.64~2.17 * 6.75 + I.33 * 6.60 f 1.07 * o.90+ I.60 *

* Significantly different (Student’s t-test) from respective controls (p < o.o~).

SD

IIY

to Wolff and Perry (1974). For each blood sample SCE were analyzed in at least 30 differentially stained cells with 46 chromosomes. Statistical methods The data concerning the mean numbers of SCE, age, period of employment, cigarette consumption and various exposed groups were evaluated with Student’s t-test.

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Results and discussion

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Table 1 shows the mean number of SCEs/cell, and the standard deviation (SD) of the total of exposed and control subjects. There is a significant difference ( p < 0.001) in the SCE frequencies between the exposed and the control subjects. A significant increase (p < 0.001) in the mean number of SCEs was found for smoking exposed personnel as compared to smoking controls. Smoking controls had fewer SCEs than occupationally exposed subjects who smoked (P < 0.01). Table 2 shows the frequencies of SCEs in exposed personnel correlated with age, occupation, duration of exposure and smoking habits. Although the SCE frequencies seemed to be

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Fig.

2. Correlation

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1

14

16

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20

22

24

26

26

30

(year)

between

the duration

of occupational

exposure and the mean number of SCEs.

higher among exposed smokers than exposed non-smokers, this difference was not significant. However, the correlation between the duration of occupational exposure and the SCE frequency was significant (p < 0.05) as shown in Fig. 1. The mean values of SCEs in exposed anaesthesia unit technicians who had a longer period of occupa-

10 6

9

0 7I

Unexposed m

Fig. 1. Frequency

Operotmg

controls Smoker

0

room

personnel

Non-smoker

of mean SCEs/cell

in SO unexposed con-

trols and h7 operating room personnel.

DSmoker

Fig. 3. Distribution and 67 operating

0

of SCEs/cell

Non-smoker

for SO unexposed controls

room personnel (IX anaesthetists M.D..

2’1

anaesthesia unit technicians, 20 anaesthesia nurses) according to their smoking habits.

tional exposure were significantly higher (P < 0.01) than the values in anaesthesia nurses. Again smokers and non-smokers differed significantly (p < 0.05) in these groups (Table 2). No significant relationship was found between age and SCEs. Smoking plays a causative role in the higher incidence of SCEs observed in both controls and the exposed group. Increased levels of SCE in peripheral lymphocytes of smokers have been confirmed by various reports (Ghosh and Ghosh, 1987; Sarto et al., 1987; !$ardaS et al., 1991). The increased frequency of SCEs in anaesthesia unit technicians, who had a longer period of occupational exposure than anaesthesia nurses, points to the importance of the duration of occupational exposure to waste anaesthetic gases. In conclusion, the present study differs from previous SCE studies by Husum et al. (Husum and Wolf, 1980; Husum et al,, 1981, 1983, 1985b, 1986) with negative results concerning the SCE test in exposure to inhalation anaesthetics. Since the level and duration of exposure, biological factors and protective measures taken vary in the different studies, a comparison between them is difficult. The elevated SCE level in operating room personnel exposed to waste anaesthetic gases (mostly halothane, nitrous oxide and isoflurane) indicates a possible genotoxic hazard so that careful measures should be taken to minimize exposure. Acknowledgements

We wish to thank Ankara University, Faculty of Medicine, Dept. of Anaesthesia for helpful contribution and special thanks to Giilseren CJlingir for secretarial assistance. References Baden, J.M., and V.F. Simmon (1980) Mutagenic effects of inhalation anaesthetics, Mutation Res., 75, 169. Baden, J.M., M. Kelly, R.S. Wharton, B.A. Hitt, V.F. Simmon and R.I. Mazze (1977) Mutagenicity of haiogenated ether anaesthetics, Anesthesiology, 46, 346-350. Baden, J.M., M. Kelly, V.F. Simmon, S.A. Rice and R.I. Mazze (1978) Fluroxene mutagenicity, Mutation Res., 58, 183.

Ghosh, R., and P.K. Ghosh (1987) The effect of tobacco smoking on the frequency of sister chromatid exchanges in human lymphocyte chromosomes, Cancer Genet. Cytogenet.. 27, 15-19. Husum, B., and H.C. Wulf (1980) Sister chromatid exchanges in lymphocytes in operating room personnel, Acta Anaesthesiol. Stand., 24, 22-24. Husum, B., H.C. Wulf and E. Niebuhr (1981) Sister chromatid exchange in lymphocytes after anaesthesia with halothane or enflurane, Acta Anaesthesiol. Stand., 25, 97-98. Husum, B., H.C. Wulf and E. Niebuhr (1982) Sister chromatid exchanges in human lymphocytes after anaesthesia with fluroxene, Br. J. Anaesth., S4,987-990. Husum. B., E. Niebuhr, H.C. Wulf and I. Norgaard (1983) Sister chromatid exchanges and structural chromosome aberrations in lymphocytes in operating room personnel, Acta Anaesthesiol. Stand., 27, 262-265. Husum, B., H.C. Wulf, E. Niebuhr, A. Kyst and N. Valentin (1984) Sister chromatid exchanges in lymphocytes of humans anaesthetized with isoflurane, Br. J. Anaesth., 56, 559-564. Husum, B., N. Valentin, H.C. Wulf, A. Halaburt and E. Niebuhr (1985a) Sister chromatid exchanges in cigarette smokers; effects of halothane, isoflurane and subarachnoid blockade, Br. J. Anaesth., 57, 1100-1103. Husum, B., H.C. Wulf and E. Niebuhr (1985b) Monitoring of sister chromatid exchanges in lymphocytes of nurse anaesthetists. Anesthesiology, 62, 475-479. Husum, B., H.C. Wulf, F. Mathiassen and E. Niebuhr (1986) Sister chromatid exchanges in lymphocytes of dentist and chairside assistants: no indication of mutagenic effect of exposure to waste nitrous oxide, Community Dent. Oral Epidemiol., 14. 148-151. Sardaa, S., S. G6k and A.E. Karakaya (1991) Increased frequency of sister chromatid exchanges in the peripheral lymphocytes of cigarette smokers, Toxicol. in Vitro, 5, 183-191. Sarto. F., L. Mustani, D. Mazzotti, R. Tomanin and A.G. Lewis (1987) Variation of sister chromatid exchange frequencies in peripheral lymphocytes of ex-smokers, Mutation Res., 192, 157-162. Spence, A.A., and R.P. Knill-Jones (1978) Is there a health hazard in anaesthetics practice?, Br. J. Anaesth., 50, 713719. Vessey, M.P.. and J.F. Nunn (1980) Occupational hazards of anaesthesia, Br. Med. J., 281, 696-698. Waskell, L. (1978) A study of the mutagenicity of anesthetics and their metabolites, Mutation Res., 57, 141. White, A.E.. S. Takehisa, I.E. Eger, S. Wolff and W.C. Stevens (1979) Sister chromatid exchanges induced by inhaled anesthetics, Ant:.thesiology, 50, 426. Wolff, S., and P. Perry (1974) Differential Giemsa staining of

sister chromatids and the study of SCE autoradiography, Chromosoma, 48, 341-353.

without

Sister-chromatid exchanges in operating room personnel.

Sister-chromatid exchange (SCE) analysis was carried out in 67 operating room personnel (anaesthetists M.D.; anaesthesia nurses and anaesthesia unit t...
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