RAPID PRODUCTION OF HYPERPLASTIC LIVER NODULES IN RATS TREATED WITH CARCINOGENIC CHEMICALS

The rapid induction of hyperplastic liver nodules by treatment with diethylnitrosamine (DEN) followed by administration of several kinds of chemicals and hepatectomy was studied in male Sprague-Dawley rats. Rats were injected with 200mg/kg body weight of DEN intraperitoneally and 2 weeks later a second chemical (N-2-fluorenylacetamide (2-FAA), 3'-methyl-4-(dimethylamino) azobenzene (3'-Me-DAB), dimethylnitrosamine (DMN), DEN, DL-ethionine, quinoline, 5, 7-dibromo-8-hydroxyquinoline, 8-hydroxyquinoline, or 8-nitroquinoline) was administered for 2 weeks, and partial hepatectomy was performed at the end of the third week of the experiment. Significant difference in the number of hyperplastic nodules was found in groups treated with 2-FAA, 3'-Me-DAB, DEN, DMN, DL-ethinonine, or quinoline compared with the control group. In groups treated with the same experimental design but without partial hepatectomy, no significant difference in the number of hyperplastic nodules was found. Continuous administration of each of the above chemicals for 4 weeks, with or without partial hepatectomy, also did not induce a significant number of hyperplastic nodules.<br>Histochemically, γ-glutamyltranspeptidase (γ-GTPase) (EC 2.3.2.1) was demonstrated in hyperplastic nodules but was absent in non-hyperplastic areas. The activities of acid phosphatase (EC 3.1.3.1), glucose-6-phosphatase (EC 3.1.3.9), and adenosine triphosphatase (ATPase) (EC 3.6.1.3) were demonstrated in non-hyperplastic areas but were low or deficient in hyperplastic nodules. γ-GTPase, as positive reaction, and ATPase, as negative reaction, are particularly good markers for the detection of hyperplastic nodules. The present results indicate the possible usefulness of a system consisting of 3 components as an in vivo short-term screening test for hepatocarcinogens: (1) DEN injection, (2) test chemical administration, and (3) partial hepatectomy during chemical administration.