Induction of glutathione-S-transferase and heat-shock proteins in rat liver after ethylene oxide exposure.
Defense mechanisms in rat liver against depletion of glutathione (GSH) and cellular injuries induced by ethylene oxide (EO) were studied. Rats were exposed to EO under either high dose (1300 ppm for 4 hr, once) or low dose (500 ppm for 6 hr, three times a week for 6 weeks) conditions. The hepatic content of GSH decreased dramatically after EO treatment, probably due to detoxication of EO. After the high dose treatment the hepatic GSH content fell by 90% of the control values but recovered within 10 to 15 hr. EO reacts directly with a variety of cellular macromolecules but all rats survived the exposure. Since the metabolites of EO are ethylene glycol and GSH-conjugates, the enzymatic activities of epoxide hydrolase and glutathione-S-transferase (GST) were determined. Only GST activity was found to occur after low dose chronic exposure. The defense mechanism at mRNA level was investigated using probes for GST and several heat-shock proteins (hsps). Enhanced accumulation of GST mRNA was detectable during the recovery period of rats after both high and low dose exposure to EO. Interestingly, both hsp32 (less than 40-fold) and hsp90 (less than 3-fold) mRNA increased after high dose exposure but the mRNA level of one of the major heat-shock proteins, hsp70, did not change under these conditions. Diethylmaleate, which is known to be a GSH depleter in liver, induced hsp32 mRNA only in rat liver, while hsp70 and hsp90 mRNA levels did not change when GSH was depleted. These results suggest that individual heat-shock proteins are induced in different ways under unphysiological conditions such as EO exposure.
Katoh
T
T
Department of Biochemistry, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Ohmori
H
H
Murakami
T
T
Karasaki
Y
Y
Higashi
K
K
Muramatsu
M
M
D000818:Animals; D015342:DNA Probes; D004790:Enzyme Induction / Q000187:drug effects; D005027:Ethylene Oxide / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000235:genetics; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects*; D008297:Male; D008298:Maleates / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains
D015342:DNA Probes; D006360:Heat-Shock Proteins; D008298:Maleates; D012333:RNA, Messenger; D006419:Heme Oxygenase (Decyclizing); D005982:Glutathione Transferase; C014476:diethyl maleate; D005978:Glutathione; D005027:Ethylene Oxide