Enhancing Effect of Inducers of Liver Microsomal Enzymes on Induction of Hyperplastic Liver Nodules by N-2-Fluorenylacetamide in Rats2

Abstract

The effects of inducers of liver microsomal enzymes on the induction of hyperplastic liver nodules by N-2-fluorenylacetamide (2-FAA) were studied in male F344 rats. The rats were fed a diet containing 200 ppm 2-FAA for 2 weeks and then given test chemicals for the following 8 weeks. Partial hepatectomies were performed at the end of the third week of the experiment. The compounds were tested, and their concentrations (in ppm) in the diet were as follows: 1,000 polychlorinated biph_enyls (PCB), 500 PCB, 500 PCB plus 70 3-methylcholanthrene (MCA); 500 PCB plus 500 ph_enobarbital, 70 MCA, 500 ph_enobarbital, 500 ph_enobarbital plus 500 β-naphthoflavone, and 2,500 3 - (3,5 - dichloroph_enyl) - 5, 5 - dimethyloxazollne - dione - 2,4 (DDOD). All experimental groups developed significantly greater numbers and total areas of hyperplastic nodules than did the controls. In groups treated similarly with the test chemicals but without partial hepatectomy, the numbers and total areas of hyperplastic nodules were significantly less than those in the experimental groups with partial hepatectomy. Administration of test chemicals except 2-FAA to partially hepatectomized rats did not induce hyperplastic nodules. The present results showed the early detection of the enhancing effect on induction of hyperplastic liver nodules by a system consisting of the following three procedures: 1) 2-FAA feeding, 2) administration of test chemicals, and 3) partial hepatectomy during administration of test chemicals. In this system DDOD enhanced the induction of hyperplastic nodules of the liver.