INTERINDIVIDUAL DIFFERENCES IN THE INVITRO 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 sample s 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 0.8-21.23 (1.03 +/- 0.14) nmol/min/mg protein. The activities towards 1-chloro-2,4-dinitrobenze ne (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. I n two of these samples, no activity was observed towards methylene chl oride, while alpha-, mu- and pi-class subunits were expressed in these human liver cytosolic samples. As the highest activity towards methyl ene chloride was still 1.4 times lower than the activity in rat cytoso l, the existence of the three populations seems to be of little import ance for human risk assessment.