The effects of O-acetylsterigmatocystin and related compounds on rat liver and cultured chicken embryonal liver cells.

Fine structural nucleolar changes induced in rat liver and primary tissue culture cells from 10-day-old chicken embryonal liver by O-acetylsterigmatocystin (AcO-stg), related compounds and aflatoxin B1 were compared. (1) Male Wistar rats were given a single i.p. injection of sterigmatocystin (stg), AcO-stg, and aflatoxin B1. 3 days after the injection of 15 mg/kg of stg, sporadic single cell necrosis was observed in rat liver, whereas rats treated with 8 mg/kg AcO-stg or more, and 3 mg/kg of aflatoxin B1 showed massive liver necrosis. Acetylation resulted in a marked increase in solubility in polar organic solvents. This increased solubility could play an important role in determining toxicity. (II) Treatment with the compounds with an unsaturateddelta1,2-furobenzofuranring system, such as AcO-stg, demethyl-diacetyl-stg (deMe-diAc-stg), and aflatoxin B1, resulted in nucleolar segregation and fragmentation of primary culture cells. Both parenchymal and mesenchymal cells in culture were susceptible to AcO-stg and deMe-diAc-stg, while the mesenchymal cells were more resistant to aflatoxin B1 than the hepatocytes. The inhibition of RNA synthesis in both cell types as determined in radioautography was in accordance with the electron-microscopic observations. Acetyldihydrosterigmatocystin (AcO-dihyd-stg), a saturated delta1,2-furobenzofuranring compound, was less toxic to primary tissue culture cells.