A SEQUENTIAL QUANTITATIVE STUDY OF THE REVERSIBILITY OR IRREVERSIBILITY OF LIVER HYPERPLASTIC NODULES IN RATS EXPOSED TO HEPATOCARCINOGENS

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  • 1 January 1980
    • journal article
    • research article
    • Vol. 71  (6) , 843-855
Abstract
The behavior of hyperplastic nodules following an in vivo short-term screening test for hepatocarcinogens was studied. Rats were injected i.p. with 200 mg/kg body weight of diethylnitrosamine (DEN), given basal diet containing 200 ppm of N-2-fluorenylacetamide (2-FAA) (group 1), 1000 ppm of the .alpha.-isomer of 1,2,3,4,5,6-hexachlorocyclohexane (.alpha.-BHC) (group 2) or basal diet (group 3) from week 3-8, and then given basal diet and tap water. They were subjected to partial hepatectomy at the end of week 3. A significant disappearance of hyperplastic nodules following the cessation of carcinogen treatment was observed in group 1, but not in groups 2 and 3. With .gamma.-glutamyltranspeptidase (GGTase) as a positive marker and ATPase as a negative marker, hyperplastic nodules were classified into 3 phenotypic categories; GGTase-positive and ATPase-negative, GGTase-positive and ATPase-negative. The percentages of GGTase-positive and ATPase-negative hyperplastic nodules were .apprx. 80-90% in group 1 and 70-80% in groups 2 and 3. Some hyperplastic nodules were necrotic from week 8 in groups 1 and 2 and from week 20 in group 3. The numbers of necrotic hyperplastic nodules increased with time. Hepatocellular carcinomas were found at weeks 30, 40 and 50 in group 1, and at weeks 40 and 50 in group 2. Significantly higher incidences of cancer were found in group 1 than in group 2. The hepatocellular carcinomas were classified enzyme-histochemically into 3 phenotypic categories as for hyperplastic nodules, but the percentage (20%) of GGTase-positive and ATPase-negative hepatocellular carcinomas was significantly lower than that (70-90%) of GGTase-positive and ATPase-negative hyperplastic nodules in each group.

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