Cytochrome P‐450 and Drug‐induced Spectral Interactions in the Hepatic Microsomes of Trout, Salmo trutta lacustris*

The properties of various components of a drug‐oxidizing mono‐oxygenase system in the liver of trout (Salmo trutta lacustris) were studied. The concentration of the cytochrome P‐450 was about 7 nmol/g liver wet weight when measured in the 12,000 × g supernatant and 0.2 nmol/mg protein when measured in the “microsomal” fraction. The activity of NADPH‐cytochrome c reductase was about 2000 nmol cyt. c reduced/g liver/min. measured in the homogenate and 20 nmol/mg protein/min. when measured in the “microsomal” fraction. The distribution of the cytochrome P‐450 into different centrifugal fractions indicates that it is localized in the endoplasmic reticulum. The cytochrome P‐450 present in the fish liver microsomal fraction was capable of interacting with different substances resulting in type II (aniline, n‐octylamine, cyanide) and a reversed type I (n‐butanol) spectra. Substances producing type I spectra in the rat liver microsomes, did not give any spectra (hexobarbital, SKF 525A) or gave unclassified spectral changes with the fish liver cytochrome P‐450 (bromobenzene, DDT, piperonyl butoxide). Spectral dissociation constants were calculated for aniline and n‐octylamine. Further experiments indicated that the mono‐oxygenase system in the trout liver microsomes can metabolize aminopyrine, aldrin and 3,4‐benzpyrene.