Genotoxicological Investigation of Hospital Nurses Occupationally Exposed to Ethylene Oxide.
II. HPRT Mutation Frequencies

Jenõ Major, Mátyás G. Jakab, and Anna Tompa

Department of Cytogenetics and Molecular Toxicology, National Institute of Chemical Safety,
József Fodor National Center for Public Health, Budapest, Hungary

Corresponding author: Anna Tompa, M.D., Ph.D., M.P.H.,
    NCPH - National Institute of Chemical Safety,
    P.O. Box 36, H-1450 Budapest, Hungary,
    Telephone: (+36) 1476-1111
    Fax number: (+36) 1476-1227
    E-mail adress: okbi@elender.hu

CEJOEM 2001, Vol.7. Nos.3-4.:195-208

Key words:
Ethylene oxide, genotoxicity, HPRT, lymphocytes, risk assessment, smoking

Abbreviations:
ALAT = (serum) alanine aminotransferase;
ASAT = (serum) aspartate aminotransferase;
EO = ethylene oxide;
GGT = (serum) gamma glutamyl transferase;
HPRT = hypoxanthine-guanine phosphoribosyl transferase;
3H-TdR = tritiated thymidine;
LI = labelling index;
MC = maximum concentration; 		MF = mutation frequency;
PBL = peripheral blood lymphocyte;
PHA = phytohaemagglutinin-P;
SCN = ferric-thiocyanate;
SE = standard error;
TG = 6-thioguanine;
VF = variant frequency.
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Abstract:
Since 1986 an unusual (breast) cancer cluster with 14 cases has appeared among nurses occupationally exposed to ethylene oxide (EO) used for sterilisation in the municipal hospital in Eger, Hungary. In order to demonstrate the occupational exposure of the nurses, chromosome aberration, sister-chromatid exchange as well as mutation (MF) and variant frequencies (VF) of the hypoxanthine-guanine-phosphoribosyl transferase (HPRT) loci were investigated in peripheral blood lymphocytes (PBL) of 27 nurses in Eger and that of 9 EO-exposed nurses in Budapest. Subjects with manifested neoplastic diseases at the time of the investigations were excluded. Here we present the data obtained on HPRT mutation frequencies. MF and VF were investigated by autoradiography. Data were compared to those of 94 historical and 34 age-matched female industrial controls, as well as to data of 10 and 14 hospital controls in Eger and Budapest, respectively. Ambient air EO concentrations were measured with gas chromatography by the local health authorities. Average peak EO concentrations in the ambient air samples were approx. 100-fold and 10-fold over the maximum concentration limit (1 mg/m3) in Eger and in Budapest, respectively, in each sampling time. VFs were significantly increased in both investigated groups in Eger, compared to the controls. Age, white blood cell count and hematocrit levels as confounding factors influenced the mean VFs in the nurses exposed to EO in Eger. However, smoking and drinking habits did not influence the mean VFs. The obtained data indicate that the occupational EO exposures at the measured levels can increase the mutation frequencies in the PBLs of the exposed nurses. Consequently, EO-exposure can be considered as an etiological factor of the cancer cluster in Eger.

Received:  11 November 2001
Accepted:  14  March 2002
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