Haemoglobin adducts of acrylonitrile and ethylene oxide in acrylonitrile workers, dependent on polymorphisms of the glutathione transferases GSTT1 and GSTM1

Thier, Ricarda; Lewalter, J.; Kempkes, M.; Selinski, Silvia; Brüning, Thomas; Bolt, Hermann M.

doi:10.1007/s002040050606

Cited by 49 publications

(15 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For other industrial toxicants, such as acrylonitrile, one study failed to observe any influence of GSTM1 and GSTT1 polymorphism on the levels of the hemoglobin valine carboxyethyl adducts (the acrylonitrile related adduct) and of hydroxyethyl-valine, one which, as highlighted, has multiple, yet unknown endogenous origins (Thier et al, 1999).…”

Section: Mass Spectrometry and Protein Adductsmentioning

confidence: 99%

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Rubino

Pitton

Fabio

et al. 2009

Mass Spectrometry Reviews

109

170

View full text Add to dashboard Cite

Cancer and degenerative diseases are major causes of morbidity and death, derived from the permanent modification of key biopolymers such as DNA and regulatory proteins by usually smaller, reactive molecules, present in the environment or generated from endogenous and xenobiotic components by the body's own biochemical mechanisms (molecular adducts). In particular, protein adducts with organic electrophiles have been studied for more than 30 [see, e.g., Calleman et al., 1978] years essentially for three purposes: (a) as passive monitors of the mean level of individual exposure to specific chemicals, either endogenously present in the human body or to which the subject is exposed through food or environmental contamination; (b) as quantitative indicators of the mean extent of the individual metabolic processing which converts a non-reactive chemical substance into its toxic products able to damage DNA (en route to cancer induction through genotoxic mechanisms) or key proteins (as in the case of several drugs, pesticides or otherwise biologically active substances); (c) to relate the extent of protein modification to that of biological function impairment (such as enzyme inhibition) finally causing the specific health damage. This review describes the role that contemporary mass spectrometry-based approaches employed in the qualitative and quantitative study of protein-electrophile adducts play in the discovery of the (bio)chemical mechanisms of toxic substances and highlights the future directions of research in this field. A particular emphasis is given to the measurement of often high levels of the protein adducts of several industrial and environmental pollutants in unexposed human populations, a phenomenon which highlights the possibility that a number of small organic molecules are generated in the human organism through minor metabolic processes, the imbalance of which may be the cause of "spontaneous" cases of cancer and of other degenerative diseases of still uncharacterized etiology. With all this in mind, it is foreseen that a holistic description of cellular functions will take advantage of new analytical methods based on time-integrated metabolomic measurements of a new biological compartment, the "adductome," aimed at better understanding integrated organism response to environmental and endogenous stressors.

show abstract

Section: Mass Spectrometry and Protein Adductsmentioning

confidence: 99%

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Rubino

Pitton

Fabio

et al. 2009

Mass Spectrometry Reviews

109

170

View full text Add to dashboard Cite

show abstract

“…GSTT1 is involved in the metabolism of small organic molecules such as ethylene oxide (Thier and Bolt 2000;Thier et al 1999), whereas GSTM1 is involved in the metabolism of highly reactive molecules, e.g. metabolites of polycyclic aromatic hydrocarbons (Butkiewicz et al 1999;Shields et al 1993).…”

Section: Introductionmentioning

confidence: 99%

Dependence of Papanicolaou gradings of exfoliated urothelial cells upon GSTM1 and GSTT1 polymorphism in benzidine-exposed workers of the Shanghai dye industry

Lin

Qiang

Chen

et al. 2001

Archives of Toxicology

View full text Add to dashboard Cite

The distribution of the polymorphic alleles of the genes coding for glutathione S-transferases (GSTs) M1 and T1 was compared with the results of cytological grading of exfoliated urothelial cells (Pap test) in a non-diseased high-risk group of workers formerly exposed to benzidine in the Shanghai dyestuff industry (n = 317). All subjects were genotyped for GSTT1 and M1 gene polymorphism by allele-specific PCR. Individuals were stratified according to their job and duration of exposure. A subgroup of 78 individuals with cytological gradings of grade III or higher in the Pap test showed a significant under-representation of the combination of GSTT1 0/0 and M1 0/0 genotypes compared with 238 subjects with a cytological classification lower than grade III (OR 0.55, 95% CI 0.31-0.98. P=0.04). These results suggest that neither the GSTM1 0/0 or GSTT1 0/ 0 genotype alone nor their combination had a clear association with cytopathological changes in exfoliated urothelial cells from individuals previously exposed to benzidine in Shanghai. This contradicts the results of studies indicating that the GSTM1 0/0 genotype is associated with an increased risk for bladder cancer in the general population, mostly outside China.

show abstract

“…Das Ethylenoxid wird durch die GSTT1 an L-Glutathion gebunden und kann folglich nicht mehr mit dem Hämoglobin reagieren. Untersuchungen von Thier et al bestätigen diese Befunde [56].…”

Section: Einfluss Der Gst-deletionen Auf Biomarkerunclassified

Glutathion‐S‐Transferase T1 und M1 (Genotypisierung) [Biomonitoring Methods in German language, 2004]

Krause¹,

Müller²

2012

The MAK‐Collection for Occupational Health and Safety

View full text Add to dashboard Cite

Veröffentlicht in der Reihe Analytische Methoden zur Prüfung gesundheitsschädlicher Arbeitsstoffe: Analysen in biologischem Material , 16. Lieferung, Ausgabe 2004 Der Artikel enthält folgende Kapitel: Grundlage des Verfahrens Geräte, Chemikalien, Lösungen, Gele Geräte Chemikalien Lösungen PCR‐Mastermix für 20 Proben in 50‐µL‐Ansätzen Gele Probenaufarbeitung Lagerung DNA‐Isolierung Bestimmung der Reinheit und Konzentration der DNA Vorbereitung und Durchführung der PCR PCR Elektrophorese Kalibrierung Auswertung Qualitätskontrolle Störeinflüsse Diskussion der Methode Addendum Zusätzlich benötigte Reagenzien und Geräte: Mastermixes Restriktionsenzyme Amplifikation unter Verwendung von PCR‐Beads Restriktionsanalyse der PCR‐Produkte Gelelektrophoretische Trennung Auswertung

show abstract

Haemoglobin adducts of acrylonitrile and ethylene oxide in acrylonitrile workers, dependent on polymorphisms of the glutathione transferases GSTT1 and GSTM1

Cited by 49 publications

References 19 publications

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Toward an “omic” physiopathology of reactive chemicals: Thirty years of mass spectrometric study of the protein adducts with endogenous and xenobiotic compounds

Dependence of Papanicolaou gradings of exfoliated urothelial cells upon GSTM1 and GSTT1 polymorphism in benzidine-exposed workers of the Shanghai dye industry

Glutathion‐S‐Transferase T1 und M1 (Genotypisierung) [Biomonitoring Methods in German language, 2004]

Contact Info

Product

Resources

About