Induction of γ-glutamyltranspeptidase-positive altered hepatocytic lesions by combination of transplacental-initiation and postnatal-selection



The purpose of this study was to induce in postnatal life the selective growth of altered hepatocytic populations which had been induced in utero by various chemicals. Pregnant rats of a Wistar strain were given a single dose of various chemical carcinogens on the 18th gestational day. From two months postpartum, both the mothers and offspring were given a diet containing 2-acetylaminofluorene (2-AAF) at a concentration of 0.02% for two weeks. Then, at the end of the first week after the 2-AAF feeding, a two-third partial hepatectomy was performed. All the animals were killed one week after the partial hepatectomy and were examined for the incidence of γ-glutamyltranspeptidase (GGT)-positive altered hepatocytic foci in the liver. The transplacental administration of not only a hepatic carcinogen, diethylnitrosamine (DEN) but also 7,12-dimethylbenzanthracene (DMBA), which does not usually produce hepatocellular carcinomas in adult rats, induced GGT-positive altered hepatocytes in the liver of the offspring. These hepatocytes grew into grossly visible hyperplastic nodules within a week after the two-third partial hepatectomy. The possible applicability of the transplacental initiation-postnatal selection model for the short-term assay of transplacental carcinogenicity is discussed.