Interindividual differences in the in vitro conjugation of methylene chloride with glutathione by cytosolic glutathione S-transferase in 22 human liver samples

article


Bogaards, J.J.P.

Ommen, B. van

Bladeren, P.J. van
The interindividual variation in the in vitro conjugation of methylene chloride with glutathione by cytosolic glutathione S-transferase (GST) was investigated with 22 human liver samples. In three of the samples no activity towards methylene chloride was observed. Eleven samples showed an activity ranging from 0.20 to 0.41 (0.31 ± 0.08) nmol/min/mg protein, and eight samples an activity of 0.82-1.23 (1.03 ± 0.14) nmol/min/mg protein. The activities towards 1-chloro-2,4-dinitrobenzene (CDNB) of these three groups were 1.17 ± 0.25, 1.12 ± 0.35 and 1.20 ± 0.53 μmol/min/mg protein, respectively. In nine of the liver samples, the α-, μ- and π-class GST subunits were quantified. In two of these samples, no activity was observed towards methylene chloride, while α-, μ- and π-class subunits were expressed in these human liver cytosolic samples. As the highest activity towards methylene chloride was still 1.4 times lower than the activity in rat cytosol, the existence of the three populations seems to be of little importance for human risk assessment.
Chemicals/CAS: Dinitrochlorobenzene, 97-00-7; Glutathione Transferase, EC 2.5.1.18; Glutathione, 70-18-8; Isoenzymes; Methylene Chloride, 75-09-2
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BiologyBiochemistryMedicineGeneeskundePhysiologyFysiologiePharmacologyToxicologyPathologyComparative StudyCytosolDinitrochlorobenzeneGlutathioneGlutathione TransferaseHumanIndividualityIsoenzymesLiverMethylene ChlorideSupport, Non-U.S. Gov't
TNO Identifier
64993
Repository link
https://resolver.tno.nl/uuid:9a709a22-27c2-46ab-b8a8-b4b72cdbe686
Source
Biochemical Pharmacology, 45(10), pp. 2166-2169.
Pages
2166-2169
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