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 monooxygenases, 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 1 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.