Inhibition of the human erythrocytic glutathione-S-transferase T1 (GST T1) by thimerosal.
We have investigated the interaction of thimerosal, a widely used antiseptic and preservative, with the human erythrocytic GST T1 (glutathione-S-transferase T1). This detoxifying enzyme is expressed in the erythrocytes of solely the human species and it displays a genetic polymorphism. Due to this polymorphism about 25% of the individuals of the caucasian population lack this activity ("non-conjugators"), while 75% show it ("conjugators") (Hallier, E., et al., 1993). Using our newly developed HPLC-fluorescence detection assay (Müller, M., et al., 2001) we have profiled the kinetics of enzyme inhibition in erythrocyte lysates of two individuals previously identified as "normal conjugator" (medium enzyme activity) and "super-conjugator" (very high activity). For the normal conjugator we have determined a 2.77 mM thimerosal concentration to inhibit 50% of the GST T1 activity. In the case of the super-conjugator a 2.3 mM thimerosal concentration causes a 50% inhibition of the enzyme activity. For both phenotypes a 14.8 mM thimerosal concentration results in residual enzyme activities equal to those typically detected in non-conjugator lysates. Thus, sufficiently high doses of thimerosal may be able to change the phenotypic status of an individual--at least in vitro--by inhibition of the GST T1 enzyme.
Müller
M
M
Department of Occupational and Social Medicine, Georg-August-University Göttingen, D-37073 Göttingen, Germany. mmuelle3@gwdg.de
Westphal
G
G
Vesper
A
A
Bünger
J
J
Hallier
E
E
D000891:Anti-Infective Agents, Local / Q000009:adverse effects*; D002851:Chromatography, High Pressure Liquid; D004912:Erythrocytes / Q000201:enzymology*; D005453:Fluorescence; D005982:Glutathione Transferase / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D010641:Phenotype; D011110:Polymorphism, Genetic; D013849:Thimerosal / Q000009:adverse effects*; D044465:White People / Q000235:genetics
D000891:Anti-Infective Agents, Local; D013849:Thimerosal; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase