Binding of benzo(a)pyrene and dibenz(a,h)anthracene to the Ah receptor in mouse and rat hepatic cytosols - PubMed (original) (raw)

. 1984 Apr;44(4):1426-32.

Binding of benzo(a)pyrene and dibenz(a,h)anthracene to the Ah receptor in mouse and rat hepatic cytosols

A B Okey et al. Cancer Res. 1984 Apr.

Abstract

Binding of the polycyclic aromatic hydrocarbon (PAH) carcinogens [3H]benzo(a)pyrene (BP) and [3H]dibenz(a,h)anthracene [DB(a,h)A] to components in rodent hepatic cytosols was characterized by sucrose density gradient centrifugation and by gel permeation chromatography on Sephacryl S-300. In hepatic cytosols from Sprague-Dawley rats, [3H]BP and [3H]DB(a,h)A bound to a component which sedimented at 8 to 9S under low-ionic-strength conditions, and had a Stokes' radius of 4.7 nm. The 8 to 9S component also bound [3H]-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and [3H]-3-methylcholanthrene (MC), two compounds previously established as Ah receptor ligands. In hepatic cytosols from C57BL/6J mice [a strain genetically "responsive" for induction of aryl hydrocarbon hydroxylase (AHH, cytochrome P1-450) by PAHs], [3H]DB(a,h)A bound to a component sedimenting at 8 to 9S which had a Stokes' radius of approximately 6 nm. The 8 to 9S component also bound [3H]TCDD and [3H]MC, but no direct binding of [3H]BP could be detected at 8 to 9S in hepatic cytosol from C57BL/6J mice, nor could specific [3H]BP binding to the 6 nm component be detected in C57BL/6J cytosol by Sephacryl S-300 chromatography. The 8 to 9S component was not detectable in hepatic cytosol from DBA/2J mice (genetically "nonresponsive" to AHH induction by PAHs) with [3H]BP or [3H]DB(a,h)A, nor with the previously established Ah receptor ligands [3H]TCDD or [3H]MC. In addition to binding to the 8 to 9S-6 nm component in C57BL/6J cytosols, [3H]BP, [3H]DB(a,h)A, and [3H]MC also bound extensively to a cytosolic component sedimenting at 4 to 5S with a Stokes' radius of approximately 3 nm. The 4 to 5S-3 nm component was present in hepatic cytosols from genetically nonresponsive DBA/2J mice, as well as in genetically responsive C57BL/6J mice. Binding of [3H]BP, [3H]DB(a,h)A, and [3H]MC to the 8 to 9S component in rodent hepatic cytosols was eliminated by incubation in the presence of a 100-fold molar excess of nonradioactive TCDD, whereas TCDD had no effect on binding of [3H]BP, [3H]DB(a,h)A, or [3H]MC to the 4 to 5S-3 nm component. The 8 to 9S component segregates with the Ahb allele in genetic crosses with mice, but the 4 to 5S component is not associated with the Ahb allele which governs AHH responsiveness. Specificity of chemicals that bind to the 8 to 9S component and segregation of the 8 to 9S component with the Ahb allele identify it as the Ah receptor which functions to regulate AHH induction in animals treated with PAHs.(ABSTRACT TRUNCATED AT 400 WORDS)

PubMed Disclaimer

Publication types

MeSH terms

Substances

LinkOut - more resources