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
- 111 Downloads
A hitherto unknown glutathione-S-transferase in human erythrocytes displays polymorphism: three quarters of the population (“conjugators”) possess, whereas one quarter (“non-conjugators”) lack this specific activity. A standard method for the identification of conjugators and non-conjugators with the use of methyl bromide and gas chromatography (head space technique) is described. Three substrates of the polymorphic enzyme, methyl bromide, ethylene oxide and dichloromethane (methylene chloride), were incubated in vitro with individual whole blood samples of conjugators and non-conjugators. All three substances led to a marked increase of sister chromatid exchanges (SCE) in the lymphocytes of the non-conjugators but not in those of conjugators. A protective effect of the glutathione-S-transferase activity in human erythrocytes for the cytogenetic toxicity of these chemicals in vitro is thus confirmed. Since the enzyme activity is not found in erythrocytes of laboratory animals, species extrapolations for risk assessment of methyl bromide, ethylene oxide and dichloromethane should be reconsidered.
Key wordsMethyl bromide Bromomethane Ethylene oxide Dichloromethane Methylene chloride Human erythrocytes SCE Enzyme polymorphism Glutathione-S-transferase
Unable to display preview. Download preview PDF.
- Bolt HM (1992) Zur Problematik der Risikoextrapolation am Beispiel von Dichlormethan (Methylenchlorid). In: Horst A, Norpoth K, Verkoyen C (eds) Krebsrisiken am Arbeitsplatz. Springer-Verlag, BerlinGoogle Scholar
- CEC, Commission of the European Communities (1990) Dichloromethane. In: Berlin A, Draper M, Krug E, Roi R, Van der Venne M (Eds.) The toxicology of chemicals, 1: Carcinogenicity, Vol. II. Luxembourg, pp 67–74Google Scholar
- ECETOC (1989) Technical Report No. 34: Methylene chloride (dichloromethane): an overview of experimental work investigating species differences in carcinogenicity and their relevance to man. ECETOC, BrusselsGoogle Scholar
- IARC International Agency for Research on Cancer (1986) Dichloromethane. IARC Monogr 41: 43–85Google Scholar
- IARC International Agency for Research on Cancer (1987) Overall evaluations of carcinogenicity: an updating of IARC Monographs Volumes 1–42. IARC Monogr Suppl 7Google Scholar
- NTP National Toxicology Program (1986) Toxicology and carcinogenesis studies of dichloromethane (methylene chloride) (CAS No. 75-09-2) in F344/N rats and B6C3F1 mice (inhalation studies) (Technical Report No. 306). US Department of Health and Human Services, Washington DCGoogle Scholar
- NTP National Toxicology Program (1992) Technical Report on the toxicology and carcinogenesis studies of methyl bromide in B6C3F1 mice (inhalation studies) (Technical Report No. 385). US Department of Health and Human Services, Washington, DCGoogle Scholar
- Pavkov KL, Kerns WD, Chrisp CE, Thake DC, Persing RL, Harroff HH (1988) Major findings in a twenty-four month inhalation toxicity study of methyl chloride in mice and rats. Toxicologist 2: 161 (Abstract No. 566)Google Scholar
- Tucker JD, Xu J, Stewart J, Ong T (1985) Development of a method to detect volatile genotoxins using sister chromatid exchanges. Environ Mutagen 7 [Suppl.3]: 48Google Scholar