Modulation of Hormonal Induction of Tyrosine Aminotransferase and Glucocorticoid Receptors by Aflatoxin BI and Sterigmatocystin in Reuber Hepatoma Cells1

Kmploying Reuber rat hepatoma cells, 114-11-1, the effects of aflatoxin BI (AKBi) and Sterigmatocystin (STC), which exhibit a similar cytotoxity but a marked difference in hepatocarcinogenicity, on the hormonal induc tion of tyrosine aminotransferase (TAT), on glucocorticoid receptors, and on their nuclear acceptor sites were investigated. VIH, strongly inhibited hydrocortisone-inducible TAT activity. The ICso value was 0.2 *ig/ml. AFBi also showed weak inhibitory effects on insulinand dibutyryl cyclic AMP-inducible TAT activities. In contrast, the 1C»of STC on hydro cortisone-inducible TAT activity was 3.5 Mg/ml, about 10 times higher than that of \l I?,. Dibutyryl cyclic AMPand insulin-inductions were not depressed by STC. AFBi inhibited the formation of cytosolic glucocorticoid receptorhormone complexes (GRCs) but STC did not. Moreover, AFBi, activated in vitro by the microsomal cytochrome I' -15(1system, interfered more markedly in the formation of cytosolic GRCs than STC did. Sucrose density gradient analysis of GRCs and Scatchard analysis revealed that AFBi and STC mainly impaired glucocorticoid receptors and GRCacceptor sites, respectively. The present data suggest a marked difference between AFBi and STC with regard to the inhibition of hormonal induction of liver specific enzymes.