Inducibility of hepatic CYP1A enzymes by 3-methylcholanthrene and isosafrole differs in male rats fed diets containing casein, soy protein isolate orwhey from conception to adulthood
Mj. Ronis et al., Inducibility of hepatic CYP1A enzymes by 3-methylcholanthrene and isosafrole differs in male rats fed diets containing casein, soy protein isolate orwhey from conception to adulthood, J NUTR, 131(4), 2001, pp. 1180-1188
Hepatic cytochrome P-450 (CYP)1A1 and 1A2 enzymes were studied in male Spra
gue-Dawley rats derived from 5-7 litters fed diets in which the protein sou
rce was casein, soy protein isolate or whey. At age 65 d, rats were gavaged
with corn oil (vehicle), 40 mg/kg 3-methylcholanthrene (3-MC) or 75 mg/kg
isosafrole (ISO), Hepatic expression of CYP1A1 and CYP1A2 mRNA, apoprotein
and associated monooxygenase activities were measured 17 h later. No signif
icant dietary effects were observed on basal expression of either enzyme. H
owever, interactions between diet and the two inducers (3-MC and ISO) were
observed in soy-fed rats for ethoxy- and methoxyresorufin O-dealkylase acti
vity, CYP1A1 and CYP1A2 apoprotein and mRNA (P < 0.05). The level of induct
ion of CYP1A1 mRNA and apoprotein was lower in rats fed soy diets than in r
ats fed casein diets (P < 0.05), and the level of induced CYP1A2 mRNA was l
ower in rats fed soy or whey (P < 0.05) after treatment with the aryl hydro
carbon (Ah) receptor-dependent inducer 3-MG. This was accompanied by a 50%
reduction in constitutive levels of the Ah receptor in liver cytosol of soy
-fed, relative to casein-fed rats, and a slightly smaller reduction in whey
-fed rats. Expression of the Ah receptor correlated with 3-MC-inducibility
of CYP1A1 mRNA in rats fed the three diets. In contrast, in rats induced wi
th ISO, which does not bind to the Ah receptor and induces CYP1As via diffe
rent mechanisms than 3-MG, ethoxyresorufin O-deethylase activity and levels
of CYP1A1 apoprotein and mRNA were elevated to a greater degree in soy-fed
than in casein- or whey-fed rats (P < 0.05). Moreover, after ISO treatment
, induction of methoxyresorufin O-demethylase activity, CYP1A2 apoprotein a
nd mRNA levels was observed only in rats fed soy (P < 0.05). These data sug
gest potential effects of dietary protein source on metabolism of a wide va
riety of CYP1A substrates, including environmental and dietary carcinogens,
many of which induce their own metabolism.