Development and Application of an in Vivo Medium-Term Bioassay System for the Screening of Hepatocarcinogens and Inhibiting Agents of Hepatocarcinogenesis

Abstract

The number of compounds which have been introduced into our environment is now far beyond our capacity to perform costly long-term carcinogenicity tests. For the purpose of performing mass-screening of compounds, in vitro short-term tests such as the Salmonella/microsome assay (Ames’ test) have been developed^1,2, and a variety of carcinogenic compounds have been shown to be mutagenic with an apparent good correlation^3–6. Recently, however, it has been shown that the mutagenicity results have not always correlated well to carcinogenicity⁴. Therefore, the development of an appropriate in vivo medium-term assay system which could bridge the gap between mutagenicity and carcinogenicity tests has become an urgent necessity. Use of rat liver utilizing the two-step concept for such a screening assay has the particular advantage of relatively easy quantitative detection of preneoplastic enzyme altered foci^7–10. Recent studies in this laboratory indicated that immunohistochemically demonstrated GST-P⁺ foci show good conformity to previously used hyperplastic nodules or γ-glutamyl transpeptidase-positive foci with the advantage of having far less background hepatocyte staining due to non-specific induction^11–15.