Cytochrome P-450 induction was investigated in the marmoset monkey, a non-human primate, using
dioxins as inducing agents. Animals received a single subcutaneous dose of 1.6 nmol
tetrachlorodibenzo-p-dioxin or tetrabromodibenzo-
p-dioxin/kg
body weight. Microsomal fractions were prepared from liver, lung and kidney, and homogenates were prepared from gut and adrenal glands. Anti-
peptide antibodies which bind to
CYP1A1,
CYP1A2,
CYP2B6 and
CYP3A4 in human were used to identify related forms in the marmoset. The results indicate that
CYP1A2 is constitutively expressed in liver, but not in lung, kidney, gut or adrenal gland and that
CYP1A1 is not expressed in any of these tissues in untreated animals. Treatment with
dioxin induced both
CYP1A1 and
CYP1A2 in liver, but only
CYP1A1 in lung. No induction of
CYP1A1 or
CYP1A2 was found in kidney, small intestine or adrenal glands. Methoxy-, ethoxy-, pentoxy- and benzoyloxyresorufin O-dealkylases and high affinity
phenacetin O-deethylase activities were induced in the liver, whereas
ethoxycoumarin O-deethylase and aryl
hydrocarbon hydroxylase activities were not affected by
dioxin treatment. High-affinity
phenacetin O-deethylase and
CYP1A2 apoprotein were detected only in liver, consistent with this activity being specifically catalysed by
CYP1A2.
Furafylline was found to be a competitive inhibitor of
methoxyresorufin O-demethylase activity with a Ki of 10 microM. In the lung the induction of
CYP1A1 was accompanied by 15- and 23-fold increases in
ethoxyresorufin O-deethylase and
methoxyresorufin O-demethylase activities, respectively, suggesting that both activities are catalysed by
CYP1A1. In contrast, there was no induction of aryl
hydrocarbon hydroxylase activity in lung or liver showing that, unlike in many other species, marmoset
CYP1A1 does not catalyse this reaction efficiently. The expression, distribution, induction and substrate specificities of marmoset monkey
P-450 enzymes differ from the situation found in rodents and other species, demonstrating that caution has to be exercised when making cross-species extrapolations.