The initiation of γ-glutamyltranspeptidase positive foci in the rat liver by N-hydroxy-2-acetylaminofluorene. The effect of the sulfation inhibitor pentachlorophenol

Abstract

The role of sulfation of the carcinogen N-hydroxy-2-acetyl-aminofluorene in the initiation phase of liver-tumor formation was studied in an initiation-promotion model modified from the Solt and Farber system (Cancer Res., 43, 188-191, 1983). The effect of the sulfation inhibitor pentachlorophenol on the induction by N-hydroxy-2-acetylaminofluorene of gamma-glutamyltranspeptidase positive foci of cells (regarded as a population of cells from which neoplastic cells will develop) was determined. Inhibition of sulfation did not prevent the induction of gamma-glutamyltranspeptidase positive foci in rat liver; on the contrary, an increase was observed. Since it is known that inhibition of sulfation of N-hydroxy-2-acetylaminofluorene prevents the formation of covalently-bound 2-acetylaminofluorene adducts to proteins, RNA, and DNA in the rat liver (Meerman et al., Carcinogenesis, 2, 413-416, 1981), the results from this study suggest that deacetylated, 2-aminofluorene adducts to DNA are responsible for initiation of gamma-glutamyltranspeptidase positive foci in the rat liver (because formation of these adducts is not affected by pentachlorophenol). After initiation with a single dose of N-hydroxy-2-acetylaminofluorene, proliferation of 'oval cells' was observed only 1 week after administration of the carcinogen. This was not observed in the livers of rats pre-treated with pentachlorophenol in which the largest number of foci develops. These data therefore suggest that 'oval cells' are not involved in the development of gamma-glutamyltranspeptidase positive foci.