Hexachlorobenzene-induced alterations of rat hepatic microsomal membrane function.
The time and dose-dependent effects of the in vivo administration of hexachlorobenzene (HCB), on hepatic microsomal membrane functions, were studied in female Wistar rats. Administration of HCB (100 mg/100 g b.w.) resulted in time-dependent decreases in the activity of two membrane-bound enzymes: 5'nucleotidase and Na+/K+ ATPase. HCB was found to cause a significant rise in protein tyrosine kinase (PTK) activity during the early stages of intoxication (day 2), followed by a significant decrease at 10 days, returning to control levels after 20 days of treatment. A stimulatory effect of HCB on in vitro endogenous microsomal protein phosphorylation was observed from 2 days of intoxication up to 30 days of treatment, with an important stimulation of phosphorylation at 5 days. Administration of HCB (100 mg/100 g b.w.) for 10 days caused a 50% reduction in epidermal growth factor receptor (EGF-R) ligand binding. The effects of known specific inhibitors of protein phosphatases on endogenous protein phosphorylation were studied. HCB affected the labelling of several bands, as well as the 5'nucleotidase and PTK activities, in a dose-dependent manner. In conclusion, this study indicated that the in vivo administration of HCB results in a significant alteration of membrane function.
Randi
A S
AS
Department of Human Biochemistry, School of Medicine, University of Buenos Aires, Argentina.
Sancovich
H A
HA
Ferramola de Sancovich
A M
AM
Loaiza
A
A
Krawiec
L
L
Kleiman de Pisarev
D L
DL
D015720:5'-Nucleotidase / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006581:Hexachlorobenzene / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000187:drug effects* / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D012989:Soil Pollutants / Q000494:pharmacology*
D012989:Soil Pollutants; D006581:Hexachlorobenzene; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D015720:5'-Nucleotidase; D000254:Sodium-Potassium-Exchanging ATPase