Long‐term effects of single and combined doses of DDT and PCB on drug‐metabolizing enzymes in rat liver

Abstract

Two common environmental pollutants, DDT and a polychlorinated biphenyl (PCB) mixture (Clophen A‐50), were administered ip to rats in discrete single doses (160 and 100 mg/kg, respectively) and in combination. All the enzyme activities studied were enhanced by DDT and PCB. The overall drug hydroxylation reactions, and their components, achieved maximal induction in 1 wk. The cytochrome P‐450 content of microsomes was increased nearly fourfold and NADPH‐cytochrome c reductase activity was enhanced twofold by both compounds. p‐Nitroanisole O‐demethylase was increased sevenfold by PCB and fourfold by DDT, aryl hydrocarbon hydroxylase threefold by PCB and 1.7‐fold by DDT. After 2 wk the activities began to decline. Distinct increases in enzyme activities were still detectable 1 month after a single dose. Epoxide hydratase and UDPglucuronosyltransferase activities were also enhanced in 1 wk (epoxide hydratase 2.5‐fold by both compounds, UDPglucuronosyltransferase tenfold by PCB in trypsin‐activated microsomes but only threefold by DDT). The disappearance of induction in epoxide hydratase was slower than in the mono‐oxygenases, and UDPglucuronosyltransferase still showed a trend toward increased activity 4 wk after the administration. The DDT‐enhanced UDPglucuronosyltransferase activity slightly returned toward the control level. Glutathione S‐transferase differed from the microsomal enzymes in that it was already elevated J day after the administration of both DDT and PCB. Its activity was only doubled, but the increased activity remained at almost the same level through the whole 1 month period.