Sequential quantitative studies on hyperplastic nodules in the liver of rats treated with carcinogenic chemicals

Sequential quantitative analyses were made of hyperplastic liver nodules induced by treating male Fischer rats first with diethylnitrosamine (DEN) and then with N-(2-fluorenyl)acetamide (2-FAA), alpha-isomer of 1,2-3,4,5,6-hexachlorocyclohexane (alpha-BHC), or phenobarbital. The test rats were injected ip with 200 mg/kg body weight of DEN, given basal diet containing 2-FAA, alpha-BHC, or phenobarbital from week 2 to 12, and subjected to partial hepatectomy at the end of week 3. From week 6, significantly higher percentage areas of hyperplastic nodules per unit area of liver were found in all experimental groups than in the control group. From week 8, significantly more hyperplastic nodules were found in all experimental groups than in the control group. Continuous administration of alpha-BHC or phenobarbital for 12 weeks with partial hepatectomy did not induce hyperplastic nodules. Continuous administration of 2-FAA did induce hyperplastic nodules, but the percentage areas and number of these nodules were significantly lower than in rats injected with DEN and then given 2-FAA orally, with partial hepatectomy.