Aflatoxin inhibition of glucocorticoid binding capacity of rat liver nuclei

Thomas W. Kensler, William F. Busby, Nancy E. Davidson, Gerald N. Wogan

Research output: Contribution to journalArticlepeer-review

Abstract

The effect of aflatoxin B1 on the binding capacity of rat liver cytoplasmic glucocorticoid receptors and the nuclear binding of the activated receptor complex was investigated. No alterations in the kinetics of [3H]dexamethasonccytosol receptor complex formation were noted 2 h after treatment with 1 mg/kg aflatoxin B1. However, a 33% decrease in the concentration of nuclear acceptor sites and a 24% decrease in the glucocorticoid receptor-nuclear binding equilibrium constant of dissociation was observed. This response was near maximal at 2 h and persisted for at least 36 h. Inhibition of nuclear binding capacity was directly related to aflatoxin B1 dose, with a correlation coefficient of 0.99. Actinomycin D treatment (0.1 mg/kg) resulted in a slight reduction (16%) in the concentration of nuclear acceptor sites but had no effect on the nuclear binding dissociation constant. Administration of [3H]dexamethasone to aflatoxin B1-treated rats produced a similar pattern of glucocortocoid binding distribution in vivo to that observed in vitro. No differences in [3H]dexamethasone-cytoplasmic receptor binding between control and aflatoxin B1-treated rats were found, whereas nuclear [3H]dexamethasone binding was reduced 34% by aflatoxin B1 treatment.

Original languageEnglish (US)
Pages (from-to)200-210
Number of pages11
JournalBBA - General Subjects
Volume437
Issue number1
DOIs
StatePublished - Jun 23 1976

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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