Role of the 4-5S binding protein in the induction of aryl hydrocarbon hydroxylase in the rat.

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.
AuthorsM Harris, C Kamps, S Safe
JournalCarcinogenesis (Carcinogenesis) Vol. 9 Issue 8 Pg. 1475-9 (Aug 1988) ISSN: 0143-3334 [Print] UNITED STATES
PMID3402044 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Carcinogens
  • Carrier Proteins
  • Benzo(a)pyrene
  • Cytochrome P-450 Enzyme System
  • Tetrachlorodibenzodioxin
  • Oxidoreductases
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP1A1
  • Animals
  • Aryl Hydrocarbon Hydroxylases (biosynthesis)
  • Benzo(a)pyrene (metabolism)
  • Carcinogens (metabolism)
  • Carrier Proteins (physiology)
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 Enzyme System (biosynthesis)
  • Enzyme Induction (drug effects)
  • Male
  • Oxidoreductases (biosynthesis)
  • Rats
  • Rats, Inbred Strains
  • Tetrachlorodibenzodioxin (pharmacology)

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