Induction of gamma-glutamyltranspeptidase-positive altered hepatocytic lesions by combination of transplacental-initiation and postanal-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-acetylamino-fluorene (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 gamma-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.