Sudan I (1-phenylazo-2-hydroxynaphthol) is a suspected human
carcinogen causing
tumors in the livers and urinary bladders of rats, mice, and rabbits. Here, we investigated for the first time the influence of
Sudan I exposure on the expression of several biotransformation
enzymes in the livers, kidneys, and lungs of rats concomitantly at the
mRNA and
protein levels and assayed their enzymatic activities. We also studied its effect on the formation of
Sudan I-derived
DNA adducts in vitro.
Sudan I increased the total amounts of
cytochrome P450 (P450) in all organs tested. Western blots using
antibodies raised against various P450s,
NADPH:P450 reductase, and
NAD(P)H:
quinone oxidoreductase 1 (NQO1) showed that the expression of P450 1A1 and NQO1 was induced in the liver, kidney, and lung of rats treated with
Sudan I. The higher
protein levels correlated with increased
enzyme activities of P450 1A1/2 and NQO1. Furthermore, 9.9-, 5.9-, and 2.8-fold increases in the formation of
Sudan I oxidative metabolites catalyzed by microsomes isolated from the liver, kidney, and lung, respectively, of rats treated with
Sudan I were found. The relative amounts of P450 1A and NQO1
mRNA, measured by real-time polymerase chain reaction (RT-PCR) analysis, demonstrated that
Sudan I induced the expression of P450 1A1 and NQO1
mRNA in the liver, kidney, and lung, and of P450 1A2
mRNA in kidney and lung. Finally, microsomes isolated from livers, kidneys, and lungs of
Sudan I exposed rats more effectively catalyzed the formation of
Sudan I-
DNA adducts than microsomes from organs of control rats. This was attributable to the higher P450 1A1 expression. Because P450 1A1 is playing a major role in the bioactivation of
Sudan I in rat and human systems, its induction by
Sudan I may have a profound effect on
cancer risk by this
azo dye. In addition, the induction of P450 1A1/2 and NQO1
enzymes can influence individual human susceptibility to other
environmental carcinogens and have an effect on
cancer risk.