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.
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.
Institut für Arbeitsphysiologie, Universität Dortmund, Germany.
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E
Hallier
T
T
Langhof
D
D
Dannappel
M
M
Leutbecher
K
K
Schröder
H W
HW
Goergens
A
A
Müller
H M
HM
Bolt
D004912:Erythrocytes / Q000201:enzymology*; D005027:Ethylene Oxide / Q000097:blood* / Q000633:toxicity; D005982:Glutathione Transferase / Q000097:blood*; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000097:blood* / Q000633:toxicity; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects; D008752:Methylene Chloride / Q000097:blood* / Q000633:toxicity; D011110:Polymorphism, Genetic; D012854:Sister Chromatid Exchange / Q000187:drug effects
D006842:Hydrocarbons, Brominated; D008752:Methylene Chloride; C005218:methyl bromide; D005982:Glutathione Transferase; D005027:Ethylene Oxide