Skip to main content
Log in

DNA-protein cross-links and sister chromatid exchange frequencies in lymphocytes and hydroxyethyl mercapturic acid in urine of ethylene oxide-exposed hospital workers

  • Original Article
  • Published:
International Archives of Occupational and Environmental Health Aims and scope Submit manuscript

Abstract

The lymphocytes of 25 hospital workers exposed to ethylene oxide and of a standardized control group were investigated for DNA damage (measured by alkaline filter elution) and sister chromatid exchange (SCE) frequencies. Additionally, the excretion of hydroxyethyl mercapturic acid (HEMA) in the 24-h urine of ten workers and ten control persons was determined. The peak levels of ethylene oxide in air during the first 8 min after opening of the sterilization unit were measured. Peak levels of ethylene oxide in the air of up to 417 ppm after opening of the sterilization unit were detected. In the alkaline filter elution assay we found significantly reduced elution rates in the exposed workers, indicating DNA-protein cross-links. The reduction of the elution rates through HVLP filters correlated significantly with the exposure classification (low, medium, high) (r = −0.45, P < 0.05) and the ethylene oxide peak level after opening of the sterilization unit (r = −0.42, P < 0.05). The SCE frequencies in the standardized control group were significantly elevated. With respect to (n = 78) historic control SCE values of our institute, the SCE values of the disinfectors were not significantly elevated (6.54 vs 6.27). The ethylene oxide-exposed workers did not have a greater percentage of high-frequency SCE cells. The mean HEMA concentration in the urine of the exposed workers was significantly elevated, but there were wide variations in HEMA concentrations and no correlation to ethylene oxide exposure. We conclude that the alkaline filter elution assay may be a sensitive parameter for monitoring the genotoxic damage in lymphocytes of ethylene oxide-exposed workers. Determination of the HEMA concentration in urine may be suitable for the differentiation between ethylene oxide-exposed and nonexposed groups, but not for individual biomonitoring. The result of the SCE determination indicates that the standardization of control groups with respect to sex, age, and smoking habit seems unsatisfactory. Therefore, it is recommended that in further studies control groups be constructed with respect to additional lifestyle factors. Additionally, enzyme polymorphisms — especially of glutathione transferase in the case of ethylene oxide exposure — should be taken into consideration and controlled.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Blome H (1982) Bestimmung von Ethylenoxid in der Luft an Arbeitsplätzen. Staub — Reinhalt Luft 42:282–284

    Google Scholar 

  • Brugnone F, Perbellini L, Faccini G, Pasini F (1985) Concentration of ethylene oxide in the alveolar air of occupationally exposed workers. Am J Ind Med 8:67–72

    Google Scholar 

  • Brugnone F, Perbellini L, Faccini GB, Pasini F, Bartolucci GB, DeRosa E (1986) Ethylene oxide exposure. Biological monitoring by analysis of alveolar air and blood. Int Arch Occup Environ Health 58:105–112

    Google Scholar 

  • Bundesanstalt für Arbeitsschutz (ed) (1990) Empfohlene Analyseverfahren für Arbeitsplatzvermessungen. Dokumentation. Schriftenreihe der Bundesanstalt für Arbeitsschutz — Gefährliche Arbeitsstoffe — GA 13. Wirtschaftsverlag NW, Dortmund

    Google Scholar 

  • Deutsche Forschungsgemeinschaft (1993) MAK- and BAT-Werte Liste 1993. VCH, Weinheim

    Google Scholar 

  • Doerjer G, Buchholz U, Kreuzer K, Oesch F (1988) Biomonitoring of DNA damage by alkaline filter elution. Int Arch Occup Environ Health 60:169–174

    Google Scholar 

  • Dunkelberg H, Hartmetz G (1977) Zur Belastung der Raumluft durch Athylenoxid im Bereich klinischer Sterilisationsanlagen. Zentralbl Bakt Hyg I Abt Orig B 164:271–278

    Google Scholar 

  • Elliott L, Mortimer V, Ringenburg V, Kercher S, O'Brien D (1988) Effect of engineering controls and work practices in reducing ethylene-oxide exposure during the sterilization of hospital supplies. Scand J Work Environ Health 14 (Suppl 1):40–42

    Google Scholar 

  • Föst U, Hallier E, Ottenwälder H, Bolt HM, Peter H (1991) Distribution of ethylene oxide in human blood and its implications for biomonitoring. Hum Exp Toxicol 10:25–31

    Google Scholar 

  • Fuchs J, Wullenweber U, Oesch F, Bienfait HG, Hild G (1992) DNA-Schäden gegenüber Ethylenoxid exponierten Arbeitnehmern. In: Kreutz R, Piekarski C (eds) Bericht über die 32. Jahrestagung der Deutschen Gesellschaft für Arbeitsmedizin e.V. Gentner, Stuttgart, pp 495–498

    Google Scholar 

  • Garry VF, Hozier J, Jacobs D, Wade RL, Gray DG (1979) Ethylene oxide: evidence of human chromosomal effects. Environ Mutagen 1:375–382

    Google Scholar 

  • Goch S, Baltes-Schmitz B, Müller G, Vahrenholz C, Norpoth K (1991) Ethylenoxid-Belastung von Desinfektoren an Gassterilisatoren in Krankenhäusern. In: Schuckmann F, Schopper-Jochum S (eds) Bericht über die 30. Jahrestagung der Deutschen Gesellschaft für Arbeitsmedizin e.V. Gentner, Stuttgart, pp 393–396

    Google Scholar 

  • Hallier E, Langhof T, Gansewendt B, Schröder K, Goergens HW, Peter H (1991) Enzyme polymorphism in human erythrocytes influences sister chromatid exchanges (SCE) induced by the fumigant methyl bromide. Zentralbl Hyg Umweltmed 192:355

    Google Scholar 

  • Hallier E, Langhof T, Dannappel D, Leutbecher M, Schröder K, Goergens HW, Müller A, Bolt HM (1993) Polymorphism of glutathione conjugation of methyl bromide, ethylene oxide and dichloromethane in human blood: influence on the induction of sister chromatid exchanges (SCE) in lymphocytes. Arch Toxicol 67:173–178

    Google Scholar 

  • Hansen JP, Allen J, Brock K, Falconer J, Helms MJ, Shaver GC, Strohm B (1984) Normal sister chromatid exchange levels in hospital sterilization employees exposed to ethylene oxide. J Occup Med 26:29–32

    Google Scholar 

  • Hedner Km Mitelman F, Pero RW (1984) Sister-chromatid exchanges in human lymphocytes after a non-S-phase incubation period to allow excision DNA repair-in vitro exposure to N-acetoxy-2-acetylaminofluorene and ethylene oxide. Mutat Res 129:71–76

    Google Scholar 

  • Hengstler JG, Fuchs J, Gebhard S, Oesch F (1994) Glycoaldehyde causes DNA-portein crosslinks: a new aspect of ethylene oxide genotoxicity. Mutat Res 304:229–234

    Google Scholar 

  • Högstedt B, Gullberg B, Hedner K, Kolnig AM, Mitelman F, Skerfving S, Widegren B (1983) Chromosome aberrations and micronuclei in bone marrow cells and peripheral blood lymphocytes in humans exposed to ethylene oxide. Hereditas 98:105–113

    Google Scholar 

  • IARC (1985) IARC monographs on the evaluation of carcinogenic risks to humans. Allyl compounds, aldehydes, epoxides and peroxides. Volume 36. IARC, Lyon

    Google Scholar 

  • IARC (1987 a) IARC monographs on the evaluation of carcinogenic risks to humans. Genetic and related effects: an updating of selected IARC monographs from volumes 1 to 42. Supplement 6. IARC, Lyon

    Google Scholar 

  • IARC (1987 b) IARC monographs on the evaluation of carcinogenic risks to humans. Overall evaluations of carcinogenicity: an updating of IARC monographs volumes 1 to 42. Supplement 7. IARC, Lyon

    Google Scholar 

  • Katoh T, Ohmori H, Murakami T, Karasaki Y, Higashi K, Muramatsu M (1991) Induction of glutathione-S-transferase and heat-shock proteins in rat liver after ethylene oxide exposure. Biochem Pharmacol 42:1247–1254

    Google Scholar 

  • Kautiainen A, Törnqvist M (1991) Monitoring exposure to simple epoxides and alkenes through gas chromatographic determination of hemoglobin adducts. Int Arch Occup Environ Health 63:27–31

    Google Scholar 

  • Kelsey KT, Wiencke JK, Eisen EA, Lynch DW, Lewis TR, Little JB (1988) Persistently elevated sister chromatid exchanges in ethylene oxide-exposed primates: the role of a subpopulation of high frequency cells. Cancer Res 48:5045–5050

    Google Scholar 

  • Kohn KW, Ewig RAG, Erickson LC, Zwelling LA (1981) Measurement of strand breaks and cross-links by alkaline elution. In: Friedberg EC, Hanawalt PD (eds) DNA repair: a laboratory manual of research procedures. Dekker, Basel, pp 379–401

    Google Scholar 

  • Korn M, Ndhlovu D (1991) Die Durchführung der Gefahrstoffverordnung im universitären Bereich am Beispiel von Ethylenoxidbegasungen. In: Schuckmann F, Schopper-Jochum S (eds) Bericht über die 30. Jahrestagung der Deutschen Gesellschaft für Arbeitsmedizin e.V. Gentner, Stuttgart, pp 389–391

    Google Scholar 

  • Laurent C, Frederic J, Marechal F (1982) Etude des effets cytogénétiques d'intoxication à l'oxyde d'éthylène. C R Soc Biol 176:733–735

    Google Scholar 

  • Laurent C (1988) SCE increases after an accidental acute inhalation exposure to EtO and recovery to normal after 2 years. Mutat Res 204:711–717

    Google Scholar 

  • Laurent C, Frederic J, Marechal F (1983) Increased sister chromatid exchange frequency in workers exposed to ethylene oxide. Ann Genet 26:138–142

    Google Scholar 

  • Laurent C, Frederic J, Leonard AY (1984) Sister chromatid exchange frequency in workers exposed to high levels of ethylene oxide, in a hospital sterilization service. Int Arch Occup Environ Health 54:33–43

    Google Scholar 

  • Lerda D, Rizzi R (1992) Cytogenetic study of persons occupationally exposed to ethylene oxide. Mutat Res 281:31–37

    Google Scholar 

  • Mayer J, Warburton D, Jeffrey AM, Pero R, Walles S, Andrews L, Toor M, Latriano L, Wazneh L, Tang D, Tsai WY, Kuroda M, Perera F (1991) Biologic markers in ethylene oxide-exposed workers and controls. Mutat Res 248:163–176

    Google Scholar 

  • Meyer-Falcke A, Wins E, Klaus B (1991) Umsetzung der Gefahrstoffverordnung im Krankenhaus am Beispiel “Ethylenoxid”. Zentralbl Arbeitsmed 41:76–78

    Google Scholar 

  • Oesch F, Hengstler JG, Fuchs J (1994) Cigarette smoking protects mononuclear blood cells of carcinogen-exposed workers from additional work exposure-induced DNA single strand breaks. Mutat Res 321:175–185

    Google Scholar 

  • Pemble S, Schroeder KR, Spencer SR, Meyer DJ, Hallier E, Bolt HM, Ketterer B, Taylor JB (1994) Human glutathione S-transferase theta (GSTTI): cDNA cloning and the characterization of a genetic polymorphism. Biochem J 300:271–276

    Google Scholar 

  • Perry P, Wolff S (1974) New Giemsa method for the differential staining of sister chromatids. Nature 251:156–158

    Google Scholar 

  • Popp W, Vahrenholz C, Schmieding W, Krewet E, Norpoth K (1991) Investigations of the frequeny of DNA strand breakage and cross-linking and of sister chromatid exchange in the lymphocytes of electric welders exposed to chromium- and nickel-containing fumes. Int Arch Occup Environ Health 63:115–120

    Google Scholar 

  • Popp W, Vahrenholz C, Yaman S, Müller C, Müller G, Schmieding W, Norpoth K, Fahnert K (1992 a) Investigations of the frequency of DNA strand breakage and cross-linking and of sister chromatid exchange frequency in the lymphocytes of female workers exposed to benzene and toluene. Carcinogenesis 13:57–61

    Google Scholar 

  • Popp W, Vahrenholz C, Schürfeld C, Schmieding W, Hoster M, Bach I, Norpoth K (1992 b) Investigations of the frequency of DNA strand breakage and cross-linking and of sister chromatid exchange frequency in the lymphocytes of patients with multiple myeloma undergoing cytostatic therapy with melphalan and prednisone. Carcinogenesis 13:2191–2195

    Google Scholar 

  • Popp W, Wolf R, Vahrenholz C, Radtke J, Schell C, Kraus R Brauksiepe A, Norpoth K (1994) Sister chromatic exchange frequencies in lymphocytes of oral cancer patients seem to be influenced by drinking habits. Carcinogenesis 14: in press

  • Richmond GW, Abrahams RH, Nemenzo JH, Hine CH (1985) An evaluation of possible effects on health following exposure to ethylene oxide. Arch Environ Health 40:20–25

    Google Scholar 

  • Sarto F, Cominato I, Pinton AM, Brovedani PG, Faccioli CM (1984 a) Workers exposed to ethylene oxide have increased incidence of sister chromatid exchange. In: Berlin A, Draper M, Hemminki K, Vainio H (eds) Monitoring human exposure to carcinogenic and mutagenic agents. IARC Scientific Publications No. 59. IARC, Lyon, pp 413–419

    Google Scholar 

  • Sarto F, Cominato I, Pinton AM, Brovedani PG, Faccioli DM, Bianchi V, Levis AG (1984 b) Cytogenetic damage in workers exposed to ethylene oxide. Mutat Res 138:185–195

    Google Scholar 

  • Sarto F, Törnqvist MA, Tomanin R, Bartolucci GB, Osterman-Golkar SM, Ehrenberg L (1991) Studies of biological and chemical monitoring of low-level exposure to ethylene oxide. Scand J Work Environ Health 17:60–64

    Google Scholar 

  • Schriewer L, Rigaux G, Riviere M vande, Lakhanisky T (1993) Frequency of DNA strand breakage in human lymphocytes as biomarker of occupational exposure. The Arnold O. Beckman IFCC European conference on environmental toxicology. Biomarkers of chemical exposure. 16–18 June. Munich, Germany

  • Schulte PA, Boeniger M, Walker JT, Schober SE, Pereira MA, Gulati DK, Wojciechowski JP, Garza A, Froehlich R, Strauss G, Halperin WE, Herrick R, Griffith J (1992) Biologic markers in hospital workers exposed to low levels of ethylene oxide. Mutat Res 278:237–251

    Google Scholar 

  • Sega GA, Generoso EE (1988) Measurement of DNA breakage in spermiogenic germ-cell stages of mice exposed to ethylene oxide, using an alkaline elution procedure. Mutat Res 197:93–99

    Google Scholar 

  • Seidegard J, de Pierre JW, Birberg W, Pilotti A, Peto RW (1984) Characterization of soluble glutathione transferase activity in resting mononuclear leukocytes from human blood. Biochem Pharmacol 33:3053–3058

    Google Scholar 

  • Stolley PD, Soper KA, Galloway SM, Nichols WW, Norman SA, Wolman SR (1984) Sister-chromatid exchanges in association with occupational exposure to ethylene oxide. Mutat Res 129:89–102

    Google Scholar 

  • Stout DL, Becker FF (1982) Fluorometric quantitation of single-stranded DNA: a method applicable to the technique of alkaline elution. Anal Biochem 127:302–307

    Google Scholar 

  • Tates AD, Grummt T, Törnqvist M, Farmer PB, Dam FJ van, Mossel H van, Schoemaker HM, Osterman-Golkar S, Uebel C, Tang YS, Zwinderman AH, Natarajan AT, Ehrenberg L (1991) Biological and chemical monitoring of occupational exposure to ethylene oxide. Mutat Res 250:483–497

    Google Scholar 

  • Tomkins DJ, Haines T, Lawrence M, Rosa N (1993) A study of sister chromatid exchange and somatic cell muation in hospital workers exposed to ethylene oxide. Environ Health Perspect 101 (Suppl 3):159–164

    Google Scholar 

  • van Sittert NJ, de Jong G, Clare MG, Davies R, Dean BJ, Wren LJ, Wright AS (1985) Cytogenetic, immunological, and haematological effects in workers in an ethylene oxide manufacturing plant. Br J Ind Med 42:19–26

    Google Scholar 

  • van Welie RTH (1991) Mercapturic acids in biological monitoring. Applications to 1,3-dichloropropene and other pesticides. Academisch Proefschrift. Vrije Universiteit to Amsterdam. FEBO, Enschede

    Google Scholar 

  • Wagner M, Kollorz W (1987) Arbeitsmedizinische Untersuchungen bei 7 Ethylenoxid belasteten Endoskopie-Pflegekräften. Zentralbl Bakt Hyg B 185:154–163

    Google Scholar 

  • Yager JW, Hines CJ, Spear RC (1983) Exposure to ethylene oxide at work increases sister chromatid exchanges in human peripheral lymphocytes. Science 219:1221–1223

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Popp, W., Vahrenholz, C., Przygoda, H. et al. DNA-protein cross-links and sister chromatid exchange frequencies in lymphocytes and hydroxyethyl mercapturic acid in urine of ethylene oxide-exposed hospital workers. Int. Arch Occup Environ Heath 66, 325–332 (1994). https://doi.org/10.1007/BF00378365

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00378365

Key words

Navigation