GLUTATHIONE-S-TRANSFERASE (GST) THETA-POLYMORPHISM INFLUENCES BACKGROUND SCE RATE

被引：59

作者：

SCHRODER, KR

WIEBEL, FA

REICH, S

DANNAPPEL, D

BOLT, HM

HALLIER, E

机构：

[1] Institut für Arbeitsphysiologie an der Universität Dortmund, Dortmund, D-44139

来源：

ARCHIVES OF TOXICOLOGY | 1995年 / 69卷 / 07期

关键词：

GLUTATHIONE-S-TRANSFERASE; THETA POLYMORPHISM; SISTER CHROMATID EXCHANGE;

D O I：

10.1007/s002040050205

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

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-smelting 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.

引用

页码：505 / 507

页数：3

共 17 条

[1] Filser J.G., Denk B., Tornqvist M., Kessler W., Ehrenberg L., Pharmacokinetics of ethylene in man
[2] body burden with ethylene oxide and hydroxyethylation of hemoglobin due to endogenous and environmental ethylene, Arch Toxicol, 66, pp. 175-163, (1992)
[3] Filser J.G., Kreuzer P.E., Greim A., Bolt H.M., New scientific arguments for regulation of ethylene oxide residues in skin-care products, Arch Toxicol, 68, pp. 401-405, (1994)
[4] Fost U., Hallier E., Ottenwalder H., Bolt H.M., Peter H., Distribution of ethylene oxide in human blood and its implications for biomonitoring, Human & Experimental Toxicology, 10, pp. 25-31, (1991)
[5] Hallier E., Deutschmann S., Reichel C., Bolt H.M., Peter H., A comparative investigation of the metabolism of methyl bromide and methyl iodide in human erythrocytes, Int Arch Occup Environ Health, 62, pp. 221-225, (1990)
[6] Hallier E., Langhof T., Dannappel D., Leutbecher M., Schroder K., Goergens H.W., Muller A., Bolt H.M., 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, pp. 173-178, (1993)
[7] Pemble S., Schroeder K.R., Taylor J.B., Spencer S.R., Hallier E., Bolt H.M., Ketterer B., Human glutathione transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism, Biochem J, 300, pp. 271-276, (1994)
[8] Perry P., Wolff S., New Giemsa method for the differential staining of sister chromatids, Nature, 251, pp. 156-158, (1974)
[9] Peter H., Deutschmann S., Reichel C., Hallier E., Metabolism of methyl chloride in human erythrocytes, Arch Toxicol, 63, pp. 351-355, (1989)
[10] Schroder K.R., Hallier E., Peter H., Bolt H.M., Dissociation of a new glutathione S-transferase activity from human erythrocytes, Biochemical Pharmacology, 43, pp. 1671-1674, (1992)

← 1 2 →