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 detoxication enzyme families, glutathione S-transferases (GSTs) and NAD(P)H:quinone oxidoreductase (QR) were determined in rat liver and kidney. Fischer 344 rats were given one intraperitoneal (i.p.) injection of TEL. GST activity, GST isoenzyme levels, mRNA levels of alpha class GST isoenzymes Ya1, Ya2, and Yc1 and activity of QR were determined. Treatment of rats with TEL caused a significant increase in GST activity in kidney. In kidney, the levels of all GST subunits were significantly elevated; the largest increase was a 3.2-fold increase in GST Yb1. The levels of GST Ya1, Ya2, and Yc1 mRNA also increased after injection of TEL. In liver, TEL injection resulted in decreased GST activity and lower levels of hepatic GSTs Yb2, Yb3, Ya1, and Ya2. The largest decrease was a 40% reduction of GST Ya1. In contrast, the level of liver GST Yc1 increased from day 4 through day 14 after injection of 10 mg/kg TEL and Yp was increased 1.4-fold 4 days after injection of 12 mg/kg TEL. The levels of liver mRNAs coding for alpha class GSTs Ya1, Ya2, and Yc1 were reduced 12 h after injection of TEL. The mRNA levels of GST Ya1 and Ya2 returned to basal level while Yc1 message increased to a level higher than controls 24 h after TEL injection. The increase in Yc1 protein between days 4 and 14 is consistent with the increase in the corresponding mRNA. The activity of QR was elevated 1.5-fold in kidney and 2.7-fold in liver 14 days after the injection of TEL. This report demonstrates that administration of organic lead significantly affects GST expression and QR activity in a tissue-specific and isoenzyme-specific manner. These results indicate that GST expression and QR activity are not co-regulated.