Interindividual differences in the in vitro conjugation of methylene chloride with glutathione by cytosolic glutathione S-transferase in 22 human liver samples.
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 mumol/min/mg protein, respectively. In nine of the liver samples, the alpha-, mu- and pi-class GST subunits were quantified. In two of these samples, no activity was observed towards methylene chloride, while alpha-, mu- and pi-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.
Department of Biological Toxicology, TNO Toxicology and Nutrition Institute, Zeist, The Netherlands.
J J
JJ
Bogaards
B
B
van Ommen
P J
PJ
van Bladeren
D003600:Cytosol / Q000201:enzymology; D004137:Dinitrochlorobenzene / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007206:Individuality; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008752:Methylene Chloride / Q000378:metabolism*
D004137:Dinitrochlorobenzene; D007527:Isoenzymes; D008752:Methylene Chloride; D005982:Glutathione Transferase; D005978:Glutathione