Glutathione-S-transferase (GST) theta polymorphism influences background SCE rate.

Polymorphism of glutathione S-transferase theta (GSTT1) modulates the toxicity of halogenated alkanes and epoxides in humans. The enzymatic activity of glutathione S-transferase theta and its corresponding gene is lacking in about 30% of the central European population. It has now been demonstrated that the background rate for sister chromatid exchange (SCE) is affected by this particular polymorphism. Smoking as a known inducer of SCE was taken into account. A group of GSTT1-positive subjects exhibited lower SCE rates than GSTT1-negative individuals (7.55 +/- 0.77 versus 8.74 +/- 1.24 SCE/mitosis, respectively, p < 0.005). Non-smoking GSTT1-positive individuals showed the lowest SCE rate (7.26 +/- 0.71 SCE/mitosis), significantly lower than the rates of smoking GSTT1-positive and non-smoking GSTT1-negative subjects (8.14 +/- 0.55 SCE/mitosis and 8.12 +/- 0.88 SCE/mitosis, respectively, p < 0.025 in both cases). Smoking GSTT1-negative subjects exhibited the highest SCE rates (9.28 +/- 1.3 SCE/mitosis). It is hypothesized that GSTT1 is protective against background genotoxic damage. Since ethylene oxide is a proven substrate of GSTT1, the detoxification of this epoxide arising from endogenous ethylene may modulate SCE background rates.

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.