Aflatoxin effects on glucocorticoid nuclear binding in rat liver

Aflatoxins block the glucocorticoid induction by de novo synthesis of the rat liver enzymes tyrosine aminotransferase (TAT) and tryptophan pyrrolase (TP). Glucocorticoid binding to cytosol receptors is an essential component of the induction process. This induction phenomenon is probably mediated also by interaction of glucocorticoid receptor complexes with nuclear acceptor sites. Using glucocorticoid binding as a probe of chromatin function, the ability of [³H] dexamethasone cytosol receptor complexes to bind to rat liver nuclei prepared from 100 gm adrenalectomized male Fischer rats pretreated with saline, DMSO or aflatoxin B₁ (AFB₁) [1 mg/kg, i.p., 2 hr prior to sacrifice] was investigated. The apparent concentration of nuclear binding sites (rho moles [³H] dex bound/mg DNA); measured by incubating at 0°C [³H] dexamethasone cytosol receptor complexes with nuclei isolated from the same rats, diminished 30% in AFB₁ treated rats compared to both saline and DMSO controls. K(d) values for the binding reaction are also reduced by 30% following AFB₁ treatment. Heterologous or 'cross over' experiments suggest that aflatoxin exerts its effect primarily at the nuclear level rather than on dexamethasone cytosol receptor formation. Nuclear binding capacity of aflatoxin cytosol macromolecule complexes is also being investigated.