Effects of lead on glutathione S-transferase expression in rat kidney: A dose-response study

Glutathione S-transferases (GST, EC 2.5.1.18) are a family of phase II deto xification enzymes involved in the conjugation of glutathione to a highly d iverse group of compounds. The purpose of this study was to evaluate the do se-response effects of lead acetate administration on the expression of rat kidney GST. Sprague-Dawley rats were injected with doses of lead acetate r anging from 0.11 to 114 mg/kg (0.3 to 300 mu mol/kg) for three consecutive days and sacrificed 24 h later. Kidney GST activity, GST isoform HPLC profi les, blood lead analysis, and electron microscopy were performed. A dose of 1.1 mg/kg lead acetate resulted in a blood lead level of 26 mu g/dl and pr oduced a significant increase in GST activity which continued to increase w ith dose up to 38 mg/kg. Morphological changes were detected at 3.8 mg/kg a nd increasing severity of cellular damage paralleled dose, blood lead level s, and changes in body weight. Individual GST isoforms exhibited different thresholds and maxima; rGSTP1 and rGSTM1 had thresholds of 1.1 and 3.8 mg/k g, respectively, very similar rates of increase with dose, and a maximum yi eld that was 450% above control at a dose of 38 mg/kg for both enzymes, rGS TA1 and rGSTA3 showed similar thresholds (1.1 mg/kg) and maximal fold incre ase (275%) but varied in the relative response to each dose. These results indicate that renal GST increases occur at lead levels which are environmen tally significant, that these changes precede cellular damage, and suggest that GST may serve as a tissue biomarker of lead exposure. (C) 1998 Society of Toxicology.