Distribution of Methylene Chloride in Human Blood

Thier, Ricarda; Foest, U.; Deutschmann, S.; Schroeder, Karsten; Westphal, Götz A.; Hallier, Ernst; Peter, H.

doi:10.1007/978-3-642-74936-0_53

Cited by 21 publications

(10 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, the chemically highly reactive substance methyl bromide led to practically no cytogenetic effect on the lymphocytes of conjugators due to its high affinity to the metabolizing enzyme in erythrocytes. In previous investigations in vitro, the distribution of radiolabelled ethylene oxide (Frst et al 1991) and dichloromethane (Thier et al 1991) in the cellular and plasma compartments of human blood was found to differ strikingly between conjugators and non-conjugators.…”

Section: Discussionmentioning

confidence: 94%

“…Previous investigations in our laboratory have identified a number of substrates for this polymorphic enzyme activity, namely methyl chloride (Peter et al 1989), methyl bromide, methyl iodide (Hallier et al 1990), dichloromethane (Thier et al 1991), and ethylene oxide (Ft~st et al 1991). Among these substrates, methyl bromide has the highest affinity for the glutathione transferase and can therefore be used as a standard test substrate for the identification of conjugators and non-conjugators.…”

Section: Introductionmentioning

confidence: 96%

See 1 more Smart Citation

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

et al. 1993

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 96%

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

et al. 1993

View full text Add to dashboard Cite

show abstract

“…Dichloromethane is one preferred substrate of hGSTT1-1 but not of other human GSTs [8,23], and the dichloromethane dehalogenase allows methylotrophic bacteria to grow with dichloromethane as the sole carbon source [24]. The purified bacterial dehalogenase requires glutathione (GSH) as a cofactor to transform dichloromethane into formaldehyde [25].…”

Section: Phylogenetics Of Gstt1-1 / Gstm1-1mentioning

confidence: 99%

Relevance of the Deletion Polymorphisms of the Glutathione S-Transferases GSTT1 and GSTM1 in Pharmacology and Toxicology

Bolt

Thier²

2006

CDM

Self Cite

257

181

View full text Add to dashboard Cite

Although cytosolic glutathione S-transferase (GST) enzymes occupy a key position in biological detoxification processes, two of the most relevant human isoenzymes, GSTT1-1 and GSTM1-1, are genetically deleted (non-functional alleles GSTT1*0 and GSTM1*0) in a high percentage of the human population, with major ethnic differences. The structures of the GSTT and GSTM gene areas explain the underlying genetic processes. GSTT1-1 is highly conserved during evolution and plays a major role in phase-II biotransformation of a number of drugs and industrial chemicals, e.g. cytostatic drugs, hydrocarbons and halogenated hydrocarbons. GSTM1-1 is particularly relevant in the deactivation of carcinogenic intermediates of polycyclic aromatic hydrocarbons. Several lines of evidence suggest that hGSTT1-1 and/or hGSTM1-1 play a role in the deactivation of reactive oxygen species that are likely to be involved in cellular processes of inflammation, ageing and degenerative diseases. There is cumulating evidence that combinations of the GSTM1*0 state with other genetic traits affecting the metabolism of carcinogens (CYP1A1, GSTP1) may predispose the aero-digestive tract and lung, especially in smokers, to a higher risk of cancer. The GSTM1*0 status appears also associated with a modest increase in the risk of bladder cancer, consistent with a GSTM1 interaction with carcinogenic tobacco smoke constituents. Both human GST deletions, although largely counterbalanced by overlapping substrate affinities within the GST superfamily, have consequences when the organism comes into contact with distinct man-made chemicals. This appears relevant in industrial toxicology and in drug metabolism.

show abstract

“…Approximately 60-70% of the human population are able to carry out this metabolic reaction ("conjugators"), whereas the remainder are unable to perform the conjugation ("non-conjugators") (9). Further characterization of these phenotypes revealed that GSH conjugation of the industrial chemicals dichloromethane (DCM) and ethylene oxide (EO), could only be catalysed by blood samples from the "conjugator" population (12,13). The monohalomethanes, EO, DCM and other man-made alkylhalides are widely used industrial methylating agents: fumigants, pesticides and solvents, and any polymorphic locus in humans that may be involved in their metabolism would be of epidemiological interest.…”

Section: Introductionmentioning

confidence: 99%

Purification, characterization and tissue distribution of human class theta glutathione s‐transferase T1‐1

et al. 1996

View full text Add to dashboard Cite

SUMMARYA high activity glutathione S-transferase TI-1 (GSTTI-1) towards dichloromethane was isolated from human liver cytosol and purified to homogenity in 18.5% yield with a purification .factor of 4400-fold. The GSTTI-1 was also isolated from erythrocytes, but the enzyme activity decreased rapidly in the final stages of purification. The purified GSTT 1-1-s were homo-dimeric enzymes with a subunit M, value 25,300 and pl 6.64, as confirmed by SDS-PAGE, IEF and Western blot analysis. The N-terminal amino acid sequences ofGSTTI-1 from liver and red blood cells, analyzed up to the 12th amino acid, were identical. Immunoblot analysis revealed that GSTT1-1 was also present in lung, kidney, brain, skeletal muscle, heart, small intestine and spleen, but not in lymphocytes.

show abstract

Distribution of Methylene Chloride in Human Blood

Cited by 21 publications

References 5 publications

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

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

Relevance of the Deletion Polymorphisms of the Glutathione S-Transferases GSTT1 and GSTM1 in Pharmacology and Toxicology

Purification, characterization and tissue distribution of human class theta glutathione s‐transferase T1‐1

Contact Info

Product

Resources

About