Role of the 4-5S binding protein in the induction of arylhydrocarbon hydroxylase in the rat

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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 monoxygenase, aryl hydrocarbon hydroxylase (AHH), was therefore investigated in the -4S and +4S Sprague-Dawley rats. The doseresponse 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.

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