RAPID INDUCTION OF GLUTATHIONE-S-TRANSFERASE-P IN RAT-LIVER CELLS AFTER ALLYL ALCOHOL-INDUCED PERIPORTAL INJURY

Large numbers of hepatocytes in non-injured areas of rat liver become transiently positive for glutathione-S-transferase-P (GST-P) within ho urs after induction of periportal liver cell necrosis induced by injec tion with allyl alcohol (AA). In addition, ,,transitional'' and ,,oval '' cells that appear during the restitutive phase of cellular prolifer ation in the periportal necrotic zones also express GST-P. A total of 43 female Sprague-Dawley rats (weight 143-183g) were injected intraper itoneally with 0.62 mmol/kg AA in saline on day 0, and sacrificed at 6 , 9 12, 33, 57, 81, 123 and 157 hours later. Liver tissue was examined by hematoxylin and eosin and by immunoperoxidase for GST-P expression . Approximately 50% of the midzonal hepatocytes became GST-P positive within 6-9 hours after injury with lower numbers of positive cells in the other zones of the liver. In addition, small cells taking part in the regenerative phase of the response to injury became weakly positiv e from 33 to 81 hours after injury. It is concluded that GST-P express ion in mature hepatocytes is an adaptive protective response to AA ind uced injury and that expression in regenerative cells is a reflection of the immature (fetal) phenotype of these cells. Therefore, GST-P sho uld not be considered a general marker of initiated or transformed cel ls, as has been hypothesized from models of chemical hepatocarcinogene sis.