EFFECTS OF LEAD ADMINISTRATION ON DEVELOPING RAT-KIDNEY .1. GLUTATHIONE-S-TRANSFERASE ISOENZYMES

The effects of acute and chronic exposure to lead on glutathione S-tra nsferase (GST) isoforms were determined in developing kidney in the ra t. The ontogeny of glutathione S-transferase isoforms was characterize d as were the effects of depletion of dietary calcium on glutathione S -transferase isoform profiles in control and lead-treated rats, In the acute exposure experiments, rats of 14 and 50 days of age received th ree daily injections of lead acetate (114 mg/kg) and in the chronic ex posure studies, rats received lead acetate at doses ranging from 50 to 500 ppm in their drinking water. Lead acetate administration in these chronic studies began 1 day after conception. Acute and chronic lead exposure had similar effects, causing increases in all but one glutath ione S-transferase isoform (Yb-3); these increases were markedly exace rbated by dietary calcium depletion, In all lead paradigms, GST subuni ts Yb-1 and Yp showed the largest increases-greater than 25-fold in ra ts fed a low-calcium diet, GST subunit Yb-3 showed small increases in the 14-day acute lead and the 4 week low-calcium animals and did not i ncrease in other groups. Lead-related increases in GSTs were partially reversed by transferring animals previously receiving lead to lead-fr ee water for a 4-week period. Kidneys of rats fed the low-calcium diet did not have detectable GST Yk, but in rats on this low-calcium diet that received 500 ppm lead; this GST isoform was found at levels compa rable to those in control rats fed lab chow. (C) 1995 Academic Press. Inc.