Differential induction of rat hepatic glutathione S-transferase isoenzymes by hexachlorobenzene and benzyl isothiocyanate. Comparison with induction by phenobarbital and 3-methylcholanthrene.
Male Wistar rats were treated with hexachlorobenzene, benzyl isothiocyanate, phenobarbital or 3-methylcholanthrene. Hepatic cytosolic glutathione S-transferase (GST) activity was determined with the substrates 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4-nitrobenzene, ethacrynic acid and trans-4-phenyl-3-buten-2-one. Cytosolic glutathione peroxidase activity was measured with cumene hydroperoxide. GST activity toward 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4-nitrobenzene and ethacrynic acid was enhanced by all compounds, hexachlorobenzene and 3-methylcholanthrene causing the largest and the smallest increase respectively. Trans-4-phenyl-3-buten-2-one-conjugating activity exhibited only small changes, while peroxidase activity with cumeme hydroperoxide was not changed by any of the inducing agents. GST isoenzymes were purified on S-hexylglutathione Sepharose 6B and separated by means of FPLC-chromatofocusing, to evaluate effects on the GST isoenzyme pattern. Hexachlorobenzene and phenobarbital both caused an increase in the relative amounts of subunits 1 and 3 when compared with subunits 2 and 4 respectively. For 3-methylcholanthrene only induction of subunit 1 was observed, possibly due to the relatively low induction levels of total GST activity. In benzyl isothiocyanate-treated animals, an induction of subunit 3 was found as well as an increase in the relative amount of subunit 2. Thus, benzyl isothiocyanate behaves differently from hexachlorobenzene, phenobarbital and 3-methylcholanthrene as an inducing agent of rat hepatic glutathione S-transferases.
Vos
R M
RM
Department of Toxicology, Agricultural University, Wageningen, The Netherlands.
Snoek
M C
MC
van Berkel
W J
WJ
Müller
F
F
van Bladeren
P J
PJ
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002722:Chlorobenzenes / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000235:genetics; D006581:Hexachlorobenzene / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis*; D017879:Isothiocyanates; D008099:Liver / Q000201:enzymology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013861:Thiocyanates / Q000494:pharmacology*
D002722:Chlorobenzenes; D007527:Isoenzymes; D017879:Isothiocyanates; D013861:Thiocyanates; D006581:Hexachlorobenzene; D008748:Methylcholanthrene; C031403:benzyl isothiocyanate; D005982:Glutathione Transferase; D010634:Phenobarbital