Effect of Dietary Phenobarbital, 3,4-Benzo(alpha)pyrene and 3-Methylcholanthrene on Hepatic, Intestinal and Renal Glutathione S-Transferase Activities in the Rat
Hepatic, intestinal, and renal glutathione-S-transferase activity was studied in rats exposed to the inducing agents 3,4-benzo(a)pyrene (50328), phenobarbital (50066), and 3-methylcholanthrene (56495). 3,4-Benzo(a)pyrene, phenobarbital, or 3-methylcholanthrene were administered in a synthetic diet to male Sprague-Dawley-rats for 14 days. Rats were then killed, and 100000 grams supernatant fractions from liver, kidney, and small intestine were tested for glutathione-S-transferase activity using 3,4-dichloronitrobenzene (99547), 1,2-epoxy-3(p-nitrophenoxy)propane, 1-chloro-2,4-dinitrobenzene (97007), p-nitrobenzyl-chloride (100141), and ethacrynic-acid (58548) as substrates. Significant increases in hepatic transferase activities for the following substrates were observed in phenobarbital treated versus control animals: 1,2-epoxy-3-(p-nitrophenoxy)propane (31 percent), 3,4-dichloronitrobenzene (102 percent), 1-chloro-2,4-dinitrobenzene (145 percent), p-nitrobenzylchlorides (111 percent), and ethacrynic-acid (51 percent). 3,4-Benzo(a)pyrene treatment resulted in significant increases in hepatic activity for the following substrates: 3,4-dichloronitrobenzene (41 percent), p-nitrobenzyl-chloride (58 percent), 1,2-epoxy-3-(p-nitrophenoxy)propane (59 percent), and ethacrynic-acid (30 percent). In contrast to parenteral administration, dietary phenobarbital had a greater influence on transferases in the small intestine. In no organ was the inductive spectrum of dietary 3,4-benzo(a)pyrene and 3-methylcholanthrene the same as for the parenteral route of administration. The authors conclude that the route of entry of a given xenobiotic plays an important role in the induction of the glutathione-S-transferases in various organs.