A comparison of the effects of hexachlorobenzene, beta-naphthoflavone, and phenobarbital on cytochrome P-450 and mixed-function oxidases in Japanese quail.

Abstract

Hexachlorobenzene (HCB), beta-naphthoflavone (BNF), or phenobarbital (PB) was administered to Japanese quail to determine their effects on hepatic porphyrin levels and drug-metabolizing enzymes. While HCB increased porphyrin levels, PB slightly reduced them, and BNF had no effect. HCB was an excellent inducer in quail, increasing the specific content of cytochrome P-450 to levels similar to those produced by BNF. Additional similarities between HCB- and BNF-treated quail included a comparable hypsochromic absorption shift in the CO-reduced difference spectra of cytochrome P-450 and similar effects on the activities of cytosolic glutathione S-transferase (GSH-t), biphenyl hydroxylase (BPH), and ethoxyresorufin O-deethylase (EROD). However, a differential response to HCB and BNF treatment was seen in the activities of hepatic NADPH-cytochrome P-450 reductase, epoxide hydrolase, GSH-t (microsomal), aryl hydrocarbon hydroxylase (AHH), and ethoxycoumarin O-deethylase (ECOD). The activities of NADPH-cytochrome P-450 reductase, AHH, and ECOD following treatment with HCB were similar to those found after dosing with PB. HCB caused a pattern of induction that was distinct from either BNF or PB and appeared to be a "mixed-type" inducer. The rapidity of the HCB-induced porphyrogenic response of Japanese quail, as compared to mammals, may provide unique advantages for making correlations between the in vivo metabolism of haloaromatic hydrocarbons and their effects on porphyrin metabolism.