title: Role of the 4-5S binding protein in the induction of aryl hydrocarbon hydroxylase in the rat.
abstract: Analysis of male Sprague--Dawley rat hepatic cytosol from two commercial animal laboratories for the polycyclic aromatic hydrocarbon (PAH) 4-5S binding protein showed that in one group of animals no 4-5S protein was detectable (-4S) whereas the levels of this protein were 208 +/- 57 fmol/mg cytosolic protein in the +4S rats. The role of the 4-5S binding protein in the transregulation of the cytochrome P-450-dependent monooxygenase, aryl hydrocarbon hydroxylase (AHH), was therefore investigated in the -4S and +4S Sprague-Dawley rats. The dose-response curves for the induction of hepatic microsomal AHH by 3-methylcholanthrene (MC) were indistinguishable in both +4S and -4S rats and comparable results were observed for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as an inducer. Both MC and TCDD exhibit high binding affinities for the aryl hydrocarbon (Ah) 8-9S receptor protein, whereas MC but not TCDD bound with high affinity to the 4-5S binding protein. Benzo[a]pyrene (B[a]P) binds with moderate affinity to both the Ah receptor and 4-5S binding protein and induces AHH in both -4S and +4S rats. Perylene binds with moderate affinity to the 4-5S binding protein but does not interact with the Ah receptor. This PAH was inactive as an inducer of AHH in +4S and -4S Sprague-Dawley rats. These results show that there was a correlation between the Ah receptor binding affinities of MC, B[a]P and perylene and their potencies as AHH inducers in Sprague-Dawley rats, and this corresponds to previous correlations for the induction of AHH in rat hepatoma H-4-II E cells in culture. In contrast no such correlations existed between the AHH induction potencies of these polynuclear aromatic hydrocarbons and their affinities for the 4-5S binding protein. These data, coupled with the fact that the absence of the 4-5S binding protein in the -4S Sprague-Dawley rats did not affect AHH inducibility by MC, B[a]P or perylene, suggests that the 4-5S binding protein does not play a role in the transregulation of cytochrome P-4501A1 in the rat or rat hepatoma cells in culture.
authors.affiliation: Department of Veterinary Physiology, Texas A&M University, College Station 77843.
authors.forename: M
authors.initials: M
authors.lastname: Harris
authors.forename: C
authors.initials: C
authors.lastname: Kamps
authors.forename: S
authors.initials: S
authors.lastname: Safe
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D001564:Benzo(a)pyrene / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism*; D002352:Carrier Proteins / Q000502:physiology*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D008297:Male; D010088:Oxidoreductases / Q000096:biosynthesis; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D002273:Carcinogens; D002352:Carrier Proteins; D000072317:Polychlorinated Dibenzodioxins; D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1