EFFECTS OF TRIETHYL LEAD ADMINISTRATION ON THE EXPRESSION OF GLUTATHIONE-S-TRANSFERASE ISOENZYMES AND QUINONE REDUCTASE IN RAT-KIDNEY AND LIVER

The effects of triethyl lead chloride (TEL) on the expression of two d etoxication enzyme families, glutathione S-transferases (GSTs) and NAD (P)H:quinone oxidoreductase (QR) were determined in rat liver and kidn ey. Fischer 344 rats were given one intraperitoneal (i.p.) injection o f TEL. GST activity, GST isoenzyme levels, mRNA levels of alpha class GST isoenzymes Ya(1), Ya(2), and Yc(1) and activity of QR were determi ned. Treatment of rats with TEL caused a significant increase in GST a ctivity in kidney. In kidney, the levels of all GST subunits were sign ificantly elevated; the largest increase was a 3.2-fold increase in GS T Yb-1. The levels of GST Ya(1), Ya(2), and Yc(1) mRNA also increased after injection of TEL. In liver, TEL injection resulted in decreased GST activity and lower levels of hepatic GSTs Yb-2, Yb-3, Ya(1), and Y a(2). The largest decrease was a 40% reduction of GST Ya(1). In contra st, the level of liver GST Yc(1) increased from day 4 through day 14 a fter injection of 10 mg/kg TEL and Yp was increased 1.4-fold 4 days af ter injection of 12 mg/kg TEL. The levels of liver mRNAs coding for al pha class GSTs Ya(1), Ya(2), and Yc(1) were reduced 12 h after injecti on of TEL. The mRNA levels of GST Ya(1) and Ya(2) returned to basal le vel while Yc(1) message increased to a level higher than controls 24 h after TEL injection. The increase in Yc(1) protein between days 4 and 14 is consistent with the increase in the corresponding mRNA. The act ivity of QR was elevated 1.5-fold in kidney and 2.7-fold in liver 14 d ays after the injection of TEL. This report demonstrates that administ ration of organic lead significantly affects GST expression and QR act ivity in a tissue-specific and isoenzyme-specific manner. These result s indicate that GST expression and QR activity are not co-regulated. C opyright (C) 1997 Elsevier Science Ireland Ltd.