Abstract
Polymorphism of glutathione S-transferase θ (GSTT1) modulates the toxicity of halogenated alkanes and epoxides in humans. The enzymatic activity of glutathione S-transferase θ 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.
This is a preview of subscription content, log in via an institution to check access.
References
Filser JG, Denk B, Törnqvist M, Kessler W, Ehrenberg L (1992) Pharmacokinetics of ethylene in man; body burden with ethylene oxide and hydroxyethylation of hemoglobin due to endogenous and environmental ethylene. Arch Toxicol 66: 175–163 [Erratum: Arch Toxicol 67: 230 (1993)]
Filser JG, Kreuzer PE, Greim A, Bolt HM (1994) New scientific arguments for regulation of ethylene oxide residues in skin-care products. Arch Toxicol 68: 401–405
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
Hallier E, Deutschmann S, Reichel C, Bolt HM, Peter H (1990) A comparative investigation of the metabolism of methyl bromide and methyl iodide in human erythrocytes. Int Arch Occup Environ Health 62: 221–225
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
Pemble S, Schroeder KR, Taylor JB, Spencer SR, Hallier E, Bolt HM, Ketterer B (1994) Human glutathione transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J 300: 271–276, 1994
Perry P, Wolff S (1974) New Giemsa method for the differential staining of sister chromatids. Nature 251: 156–158
Peter H, Deutschmann S Reichel C, Hallier E (1989) Metabolism of methyl chloride in human erythrocytes. Arch Toxicol 63: 351–355
Schröder KR, Hallier E, Peter H, Bolt HM (1992) Dissociation of a new glutathione S-transferase activity from human erythrocytes. Biochem Pharmacol 43: 1671–1674
Thier R, Föst U, Deutschmann S, Schröder KR, Westphal G, Hallier E, Peter H (1991) Distribution of methylene chloride in human blood. Arch Toxicol 14: 254–258
Thier R, Persmark M, Pemble SE, Taylor FB, Ketterer B, Guengerich FP (1994) Mutagenicity of 1,2,3,4-butadiene-diepoxide is altered by mammalian θ class glutathione S-transferase. Naunyn-Schmiedebergs Arch Pharmacol, Suppl. 349: R121 (abstract 482)
Törnqvist M, Gustafsson B, Kautiainen A, Harms-Ringdahl M, Granath F, Ehrenberg L (1989) Unsaturated lipids and intestinal bacteria as sources of endogenous production of ethene and ethylene oxide. Carcinogenesis 10(1): 39–41
Törnqvist M, Svartentren M, Ericsson CH (1992) Methylation in hemoglobin from monozygotic twins discordant for cigarette smoking: hereditary and tobacco-related factors. Chem-Biol Interactions 82: 91–96
Warholm M, Alexandrie AK, Högberg J, Sigvardsson K, Rannug A (1994) Polymorphic distribution of glutathione transferase activity with methyl chloride in human blood. Pharmacogenetics 4: 307–311
Wiebel FA, Schröder KR, Hallier E, Bolt HM (1995) Metabolism of epoxides and halogenated alkanes by polymorphic glutathione S-transferase theta. Naunyn-Schmiedebergs Arch Pharmacol, Suppl 351: R23 [Abstr 90]
Wiencke JK, Wrensch MR, Miike R, Petrakis NL (1991) Individual susceptibility to induced chromosomal damage and its implication for detecting exposures in human populations. Cancer Res 51: 5266–5269
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schröder, K.R., Wiebel, F.A., Reich, S. et al. Glutathione-S-transferase (GST) theta polymorphism influences background SCE rate. Arch Toxicol 69, 505–507 (1995). https://doi.org/10.1007/s002040050205
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s002040050205